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].