Case Report of Clinically Probable Sporadic Creutzfeldt-Jakob Disease from A Tertiary Care Hospital in South India

We are reporting an otherwise healthy lady of forty eight years suffering from rapidly progressive dementia, behavioural disturbances, myoclonus, ataxia and extrapyramidal features of eight months duration with characteristic abnormalities on brain imaging, electroencephalography with positive cerebrospinal fluid 14-3-3 protein, satisfying the revised World Health organization (WHO) criteria for diagnosis of “clinically probable Sporadic Creutzfeldt-Jakob disease (sCJD)”. An attempt was made to clinically differentiate the diagnostic possibilities. Case Report Case Report of Clinically Probable Sporadic Creutzfeldt Jakob Disease from A Tertiary Care Hospital in South India Shaik Afsar Pasha1, Ankamma Rao2, Phani Bhushan3, Bhaskara Rao B4 and Prasunpriya Nayak5* 1Department of Neurology, NRI Medical College, General Hospital, Chinakakani, Guntur District, Andhra Pradesh 522503, India. 2Department of Radiology, NRI Medical College, General Hospital, Chinakakani, Guntur District, Andhra Pradesh 522503, India. 3Department of Psychiatry, NRI Medical College, General Hospital, Chinakakani, Guntur District, Andhra Pradesh 522503, India. 4Department of General Medicine, NRI Medical College, General Hospital, Chinakakani, Guntur District, Andhra Pradesh 522503, India. 5Department of Physiololgy, NRI Medical College, General Hospital, Chinakakani, Guntur District, Andhra Pradesh 522503, India. Dates: Received: 08 March, 2017; Accepted: 31 March, 2017; Published: 03 April, 2017 *Corresponding author: Dr. Prasunpriya Nayak, Department of Physiololgy, NRI Medical College, General Hospital, Chinakakani, Guntur, Andhra Pradesh, 522503, India; Email:


Introduction
Sporadic Creutzfeldt-Jakob disease is the most common of the prion diseases affecting the human race [1]. Prion diseases, a group of uniformly fatal neurodegenerative diseases, caused by conformational change of PrP c (normal cellular form of prion protein) to abnormal PrP sc (abnormal scrapie of prion protein) which cumulates in various regions of the brain resulting in spongiform degeneration and gliosis [2]. In Prions are characterized by their infectious properties and by the intrinsic ability of their structures to act as a template and convert the normal physiological PrP C into the pathological disease-causing form, PrP Sc . PrP Sc acts as a template for the misfolding of PrP C into PrP Sc .
CJD can present in four forms namely sporadic (85%), familial (10-15%), iatrogenic (<1%) and variant CJD (<1%). Sporadic CJD manifests at 6 th -7 th decade with rapidly progressive dementia, behavioral dyscontrol in the form of aggressive outbursts, restlessness, irritable, delirium, hallucinations, delusions, apathy, confusional spells followed by pyramidal, extrapyramidal, cerebellar symptoms including myoclonus. The characteristic features of myoclonus includesbeing generalized, fast at a frequency of 1 per second, stimulus sensitive and non-epileptic. Ocular symptoms sometimes coexist in the form of cortical blindness, distortion of seen objects and paralysis of convergence or upgaze. Our patient has multifocal generalized myoclonus on a background of dementia, ataxia and behavioural disturbances. The Variant CJD manifests in relatively young patients with early psychiatric features, chorea, myoclonus, persistent painful paraesthesia followed by dementia. The salient features of Sporadic and Variant CJD are enlisted in (Table 1).
As already mentioned, MRI brain can be normal in the earlier stage of the disease, however, the signal alterations precede the changes in EEG and CSF abnormalities. Among the sequences, T2, FLAIR, DWI, ADC mapping has been used to detect the abnormality. DWI sequence is more sensitive (92%) and specifi c (93%). However combination of DWI and FLAIR signal changes increased the sensitivity to 98% and specifi city to 95%. DWI sequence is more sensitive in the diagnosis of CJD in its early stage independent of EEG changes. Two patterns of abnormalities were described like isolated cortical gyri hyperintensities, combined cortical and deep gray nuclear (basal ganglia) involvement and Isolated Basal ganglionic changes could have been Third pattern [4]. Most common type is pattern two. The pathological correlate of T2 and FLAIR hyperintensity is astrogliosis, while vacuole formation which restricts the water diffusion in DWI imaging. Involvement of deep gray matter is associated with shorter disease course with rapidly progressing neurologic deterioration whereas absence of basal ganglia involvement correlates with delayed onset of dementia and longer disease course [5]. Combined DWI and FLAIR has higher sensitivity (91%) and specifi city (95%) for CJD [6]. However, Vitali et al reaffi rms that the pattern of FLAIR/DWI hyperintensity and reduction of ADC in striatal hyper intensity regions on DWI differentiates sporadic CJD from other rapidly progressive dementia with 98% sensitivity and 100% specifi city [7].

Case Report
48 year old lady, mother of 2 children, uneducated, right

Discussion
This patient was diagnosed as clinically probable CJD inview of rapidly progressive dementia, cerebellar ataxia and cortical myoclonus, disease duration of less than 2 years, EEG abnormality and MRI brain abnormality, which is compatible with the diagnosis of CJD.
The age at onset of the disease was relatively younger in our case as similar to the published cases by Mehndiratta et al. [8]. The female preponderance among the published case series was also reported by Mehndiratta et al. [8]. Our patient had the typical clinical manifestations like rapidly progressive dementia, myoclonus, ataxia, tremors and behavioural symptoms. Similar observations were noted in the case series by Velásquez-Pérez et al. [9] and GonzálezDuarte et al. [10]. Behavioural manifestations in CJD occur in 30% of patients at the onset and 57% at later stages of the disease [1]. Mahale et al. found 62% of their patients having behavioural manifestations [11]. Our patient did not have any family history, hence we presume this as sporadic CJD. Familial CJD was reported only in 2 cases by González Duarte et al [10], and single reports by Mehndiratta et al. [8] and Chandra et al. [12]. The time interval between the onset of the symptoms to the diagnosis was 8   months in our case while it ranges from 1-12 months in other case series [8,10]. As per the literature, the mean duration from onset of symptoms to the time of death was 6.6 months (Range: 3-14 months) [8,10]. The mean survival of CJD patients is 5 months and about 80% of patients succumb to disease after 12 months from onset [1]. Our patient is alive and dependent on care givers for her daily functioning.
EEG in our patient showed triphasic waves and periodic sharp wave complexes, however, it can be normal in the earlier part of the disease but classical features would be generalized periodic sharp waves, biphasic and triphasic waves at a rate of one per second. EEG has a sensitivity of 67% and specifi city of 7486% in the diagnosis of CJD [10]. Repeated EEG during the course of disease increases the probability of demonstrating characteristic EEG abnormality.Similar EEG fi ndings is sometimes possible in Hashimotos encephalopathy and VGKC encephalitis but easily can be differentiated as illustrated in (Table 2).
Imaging study of the current patient revealed abnormality The detection of the 14-3-3 protein in CSF has been one of the markers for diagnosis of CJD [14]. This protein detection raises the accuracy in diagnosing sporadic CJD with sensitivity of 92% and specifi city 80% [15]. But Zerr et al.
refuted this observation as they found that imaging fi ndings were equivalent to elevated levels of the 14-3-3 protein in the diagnosis of probable sporadic CJD [16]. Other biomarkers such as ttau, p-tau, S-100, or neuron-specifi c enolase (NSE) in the CSF are required in addition to, protein 14-3-3 [15].

Diagnosis
The diagnosis is based on clinical profi le of the onset and course of symptoms, EEG changes and typical imaging abnormalities. Several clinical criteria exist, but the better bedside one is the CDC`s Clinical criteria for diagnosis of CJD 2010 which is the Revised WHO criteria (Table 3) [17]. Of late, other than CSF 14-3-3 which is a surrogate marker for the diagnosis of CJD, several other markers like Neuron specifi c enolase (NSE), S-100 beta amyloid, p-tau, t-tau are available.
Focusing the possibilities of early detection of prion diseases, recently, anti-prion screening test using real time quacking-induced conversion has been reported [18]. Though, olfactory epithelium is a known peripheral target of PrP SC deposition in sCJD [19], CSF and urine are also reliable source for early detection of sCJD [20], whereas, a new blood test has been recently identifi ed with 100% sensitivity and specifi city in vCJD [21]. Yield of different diagnostic tests is enlisted in the (Table   4).

Conclusion
High index of suspicion is required to identify the patients with classical manifestations so as to register to the national authority and to take necessary preventable action, if possible, and to treat symptomatically in view of lack of defi nite curative treatment at present for this fatal disease. Iatrogenic CJD: Progressive cerebellar syndrome in a recipient of human cadaveric-derived pituitary hormone; or sporadic CJD with a recognized exposure risk, e.g., antecedent neurosurgery with dura mater graft Familial CJD: Defi nite or probable CJD plus defi nite or probable CJD in a fi rstdegree relative; and/or neuropsychiatric disorder plus disease-specifi c PrP gene mutation.