Discussion
While Creutzfeldt-Jakob disease has a multifaceted clinical presentation that differs based on which areas of the brain are most affected, rapidly progressive cognitive decline is a particularly typical finding. Thus, the differential diagnosis should always include conditions that manifest with a syndrome of rapidly progressive dementia. Primarily, certain treatable and/or reversible diseases, such as paraneoplastic and autoimmune encephalitis, viral encephalitis, metabolic encephalopathy, HIV, and Lyme disease should be considered [13]. Primary CNS lymphoma, vasculitis, and intravascular lymphoma can also lead to rapidly progressive dementia. MRI is usually helpful in confirming or excluding these diagnoses. Mitochondrial encephalopathy with lactate acidosis and stroke-like episodes (MELAS) can have some clinical features overlapping with CJD, however it presents in a younger population and appears on imaging as multifocal cortical-subcortical lesions resembling strokes of various ages with typical elevated lactate on MR spectroscopy [14]. Other dementias such as Alzheimer’s disease, dementia with Lewy bodies, frontotemporal dementia, corticobasal degeneration, and progressive supranuclear palsy usually progress less quickly and on imaging are characterized by atrophy in a generalized or specific distribution, without the extensive diffusion restriction typically found in CJD [15].
In our case the patient’s rare main condition (sCJD) was complicated by what we assume to be an infrequent process of a completely different etiology (NMS, a complication of antipsychotic medication), which made the differential diagnosis after its onset more difficult. Various predisposing factors, including organic brain diseases, are postulated to exert influence on the development of NMS [16]. Therefore, we might hypothesize that structural changes in the brain (particularly in the caudate nuclei and putamina) caused by CJD could have contributed to a disruption of nigrostriatal pathways and a decrease in dopaminergic activity, which could have resulted in a hypersensitivity to antipsychotic drugs and therefore a predisposition to develop NMS.
The risk of NMS may increase with extrapyramidal disorders such as PD [17]. This type of neuroleptic sensitivity is broadly described in patients with dementia with Lewy bodies (DLB), hence additional studies are essential to differentiate these conditions to avoid false positive diagnosis of CJD, as was shown in a case series by Lemstra et al., in which they described 12 patients with autopsy-confirmed DLB who had been clinically suspected to suffer from CJD; however, our case shows that a manifestation of neuroleptic sensitivity can also occur in CJD [18].
According to Yang et al. study of 173 sCJD cases, extrapyramidal symptoms were noticed in over 77% of patients and were the second most frequent symptom after progressive dementia. [19].
Diffusion restriction (which correlates with spongiform changes detected on autopsy) in the basal ganglia (particularly caudate nuclei and putamina) is found in a great proportion of CJD cases, although to our knowledge there are no other reports about CJD and NMS co-existing [20; 21]. We emphasize the diagnostic dilemma of this case: whether persisting extrapyramidal hypertonia, reduced consciousness, and dysautonomia after treatment of NMS were residual symptoms of incompletely resolved NMS, or a consequence of the inevitable progression of CJD.
Disease duration in presented case was about five months. According to the collaborative study of human transmissible spongiform encephalopathies, mean survival time of sCJD is 7,3 months, median - 5 months [22]. Unfortunately, we cannot confidently affirm whether shortened survival time and fast progression of the disease was due to NMS. There is limited amount of data concerning the survival time in patients with CJD. Younger age, female sex, clinical manifestation of cerebellar symptoms, pseudo-periodic sharp-wave complexes on EEG and presence of various biomarkers in CSF were reported to be factors of longer survival time [23; 24].