Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, invariably fatal neurodegenerative disease which is caused by deposition of an abnormal isoform of a cellular glycoprotein known as the prion protein [1]. The word prion means proteinaceous infectious particle. Misfolding of prion protein leads to formation of prion protein scarpie (PrPSc) which form insoluble aggregates in the brain tissue. Deposition of prion protein scarpie (PrPSc) leads to neuronal loss and cause small vacuoles formation and spongiform appearance of the cerebral cortex [2]. The annual incidence of human prion disease is one or two per million [3]. Creutzfeldt-Jakob disease (CJD) is the most common human prion disease. It is classified into three categories: sporadic, acquired or familial [3]. Sporadic CJD (sCJD) constitutes for 85% of total CJD cases [2]. The mean age of onset of sCJD is in the sixth decade and both genders are equally affected [2]. Centre of Disease Control proposed three categories of diagnostic certainty of sCJD: definite, probable and possible. Definite sCJD depends on either on neuropathological finding or detection of prion protein scarpie PrPSc or scrapie- associated fibrils in the brain tissue. Probable and possible diagnosis of sCJD is based on clinical neurological findings, specific EEG findings, CSF biomarkers and distinctive MRI findings [4]. sCJD represents multifocal neurological findings such as rapidly progressive dementia, myoclonus, ataxia, pyramidal / extrapyramidal signs, visual disturbances, cerebellar signs. Additional signs include behavioural dysfunction, and primitive reflexes. The disease follows a rapidly progressive state of akinetic mutism in the later stage. About 80% patients die within 12 months of disease onset [2]. We present a case report of a 69 year old female who was admitted with recurrent fall,progressive unsteadiness and intermittent confusion over 5 weeks.

A 69-year-old female presented with recurrent falls. Patient has background of alcohol excess and hypercholesterolemia. Her husband reported gradual worsening unsteadiness and intermittent confusion over the past 5 weeks. Routine blood tests were normal, so patient was treated for alcohol excess. Two days after admission, patient started having myoclonic jerks in ankles, tremors, increased tone in lower limbs bilaterally and slurred speech and ataxia. CT-head was negative. CSF analysis was normal apart from mildly elevated protein level of 90 mg/dl. She was started on aciclovir for working diagnosis of encephalitis. An extensive workup was performed. This included MRI-DWI of the brain and cervical spinal MRI, CT of the chest & abdomen, liver autoantibodies, vasculitis screen and Willson’s disease screen. These investigations were inconclusive. Neurology advice was sought, and other tests were recommended like EEG, repeat lumber puncture and autoimmune encephalitis screen. EEG demonstrated symmetrical background without typical  sharp wave complexes. Other tests were normal and repeat CSF showed protein level (50mg/dl). Patient continued to have aciclovir. Patient then started to develop dysarthria, myoclonic jerking of all limbs, and fixed right gaze then gradually became drowsier and confused. She was transferred to the intensive care unit (ICU) due to deteriorating GCS, but she did not require any ventilation or inotropes. MRI head was repeated which showed high T2 signal changes in basal ganglia and thalamus with restricted diffusion. There was bilateral frontal cortical ribboning which was highly suspicious case of sCJD. National CJD Research and Surveillance Unit in Edinburgh was contacted and advised to store CSF in the lab then a team came to review the patient. They suggested palliative care for the patient. Patient’s CSF was positive for Real-time-quaking-induced conversion (RT-QuIC). Patient was finally discharged with proper support and care by the community palliative care team. As per our knowledge patient is still alive.

Based on the CDC’s diagnostic criteria for sCJD [4] our patient was diagnosed with probable sCJD with key findings of myoclonus, pyramidal signs, extrapyramidal signs (tremor), and rapidly progressive neuropsychiatric deterioration, high T2 signal change in basal ganglia and bilateral frontal cortical ribboning, and RT-QuIC positive in CSF. Patient was having gradually progressive unsteadiness and intermittent confusion over five weeks before attending the hospital, which might be representing the early stage of the disease. According to Iwasaki [3], the first stage of sCJD consists of non-specific symptoms such as anxiety, depression, visual disorder, memory disturbance and unsteadiness. Within a very short time after admission the patient was representing progressively deteriorating altered sensorium, developed myoclonus, pyramidal and extrapyramidal signs which were indicative of progression to the second stage of the disease as described in [3]. It is remained unclear why our patient was showing fluctuating GCS score. CSF assay for Real-time quaking-induced conversion was positive in our patient. The sensitivity and specificity of CSF RT-QuIC were 92% & 100%, respectively. This is according to a research undertaken by  the UK National CJD Research & Surveillance Unit [5]. Our patient did not represent typical EEG findings of sporadic CJD. Her EEG demonstrated symmetrical background without the typical sharp wave complexes. According to a study [6], characteristic periodic sharp wave complexes (PSWCs) are prevalent during the second phase of the disease, usually about 3 months after the initial presentation. However, our patient presented to us in her fifth weeks’ of symptoms onset as cited by her husband and she had EEG investigated on the fourth day of hospital admission. Although, the periodic EEG pattern is characteristic and consistent with CJD, it is not pathognomonic. Evidence of PSWCs during EEG recording is associated with a sensitivity of 67% and specificity of 86% for detection of sCJD [6]. MRI plays a crucial role for diagnosis of sCJD. Sensitivity and specificity of typical MRI findings for diagnosis of sCJD are 83-92% and 87-95%, respectively. Cortical involvement in sCJD is the commonest finding in MRI. The second most common area involved is the basal ganglia. In about 13% of cases of sCJD, nonspecific thalamic hyperintensity is represented. Our patient represented almost all of the typical MRI diagnostic criteria of probable sCJD [7]. We have done repeated MRI with 10 days interval as the initial MRI finding was inconclusive and the repeated MRI head was suggestive of highly suspicious sporadic CJD. The hyper intensity in MRI is very subtle or not detectable in early phases of sCJD [7]. This case emphasizes that repeated assessment and diagnostic test may be required to diagnose sCJD. We have done extensive workup to rule out the differential diagnosis. We ruled out possibility of paraneoplastic, autoimmune encephalitis, hepatic encephalopathy and Willson’s disease. Our patient was treated with acyclovir for a period of time with clinical suspicion of encephalitis. However, this case illustrates that uncommon and rare etiologies must be considered in cases of unexplained and rapidly progressive neurological decline. Hence, more clinical awareness and diagnostic skills are necessary to differentiate sCJD from other similar neurological conditions.

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