Background
Case presentation
Clinical follow-up
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Month 0: A 44 year-old man, 12 years of education, started complaining acutely of slowness and sustained attention difficulties. He had neither clinical comorbidities nor relevant familial history.
M0 | M2 | M7 | M15 | M27 | M43 | ||
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Neuropsychological assessment
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Global cognitive state
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MMSE | 25 | 25 | 24 | 21 | 17 | 13 | |
Speed processing
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TMT part A, time (seconds) | 133 | 157 | 144 | 193 | NA | NA | |
Short term memory
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WAIS III digit span forward | 4 | 5 | 5 | 5 | 3 | NA | |
WAIS III digit span backward | 3 | 3 | 2 | 3 | 2 | NA | |
Executive functions
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Phonemic verbal fluency: letter ‘p’ | 12 | 1 | 6 | 10 | NA | NA | |
Semantic verbal fluency: ‘animal’ category | 15 | 16 | 16 | 12 | NA | NA | |
FAB (/18) | 12 | 12 | 12 | 10 | 6 | 2 | |
TMT part B, time (seconds) | 296 | 537 | 486 | NA | NA | NA | |
TMT part B, mistakes | 0 | 1 (help) | 1 | ||||
Anterograde verbal memory
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FCSRT | |||||||
sum of free recalls (/48) | 19 | 18 | 27 | 22 | 8 | NA | |
sum of free + cued recalls (/48) | 42 | 47 | 46 | 45 | NA | NA | |
recognition (/48) | 47 | 48 | 48 | 45 | NA | NA | |
delayed free recall (/16) | 9 | 6 | 8 | 6 | NA | NA | |
delayed free + cued recall (/16) | 14 | 14 | 16 | 15 | NA | NA | |
Anterograde visual memory
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Rey complex figure, memory (/36) | < centile 10 | - | - | - | NA | NA | |
Language
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DO80 (/80) | - | - | 60 | - | NA | NA | |
Visuoconstructive praxies
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Rey complex figure, copy (/36) | 25 | 12 | 13.5 | - | NA | NA | |
EEG
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Slow cerebral activity No epileptic or pseudo-periodic abnormalities | - | PSWC discharges during hyperpnea | unchanged | - | - |
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Month 2: His condition worsened, and he was hospitalized in the Department of Neurology, in University Hospital, Toulouse, France. In the absence of sustained stimulation, the patient remained motionless and speechless, due to severe apathy. Falls occurred frequently (about once a day), due to altered postural reflexes. After marked stimulation, it was noticed that the patient was depressed but not melancholic or suicidal. Marked symmetric and axial parkinsonian syndrome did not improve after L-dopa challenge. Slight reflex myoclonus was noticed in the upper limbs. Ocular saccades were slow but not limited. Apraxia and executive dysfunctions had worsened. Detection of 14–3–3 protein performed from cerebrospinal fluid (CSF) sample by western-blot was positive, whereas cytology and biochemistry were normal. Structural cerebral MRI revealed fronto-temporal atrophy on visual assessment of T1 sequence, with no abnormality on diffusion weighted imaging (DWI). Ropinirole, and tianeptine treatments were replaced by citalopram, oxazepam and zopliclone.
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Month 6: Daily risperidone treatment was introduced due to delusions of persecution and rare visual hallucinations.
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Month 7: Parkinsonism did not deteriorate with the addition of neuroleptic agents. Delusions and hallucinations remained present, although less prominent, and cognitive functions kept worsening. Structural MRI was unchanged, and 18F-FDG-PET visual assessment showed severe hypometabolism in parietal regions.
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Month 10: The patient only experienced few hallucinations without delusions. Risperidone treatment was stopped but parkinsonian symptoms had worsened: he had severe dysarthria and was not able to walk without assistance because of his instability.
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Month 20: Axial parkinsonian symptoms had worsened: he had difficulties swallowing, severe dysarthria, freezing in narrow place and total loss of postural reflexes. He was bed-ridden most of the day. CSF 14–3–3 protein remained positive, while total-tau (238 pg/mL) and Aβ42 (511 pg/ml) levels were within the normal ranges (norm < 450 pg/mL and > 500 pg/mL, respectively).
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Month 43: Parkinsonian symptoms were very severe, and myoclonus more pronounced. Important perseverations, imitations, and grasping were reported. Speech was unintelligible. Detection of 14–3–3 protein in CSF was negative.
Imaging analyses
Histopathology
Molecular genetics
Conclusions
Dementia with Lewy bodies | Creutzfeldt-Jakob disease | Case reported | |
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Central feature | |||
Cognitive decline | Progressive, insidious onset | Acute or rapidly progressive | Acute |
Prominent or persistent memory impairment | Not early: usually evident with progression | Early | Early |
Prominent deficits of attention, executive function, and visuospatial ability | Yes | No (global dementia) | No (global cognitive impairment) |
Core features | |||
Fluctuating cognition | Yes | No | No |
Recurrent visual hallucination | Yes | Yes | No (mainly delirious with few hallucinations) |
Spontaneous features of parkinsonism | Yes | Yes | Yes |
Suggestive features | |||
REM sleep behavior disorder | Yes | No | Not reported by the wife |
Severe neuroleptic sensitivity | Yes | No | No |
Low dopamine uptake in basal ganglia on imaging | Yes | Very rare (one case reported [22]) | Not performed (the case was parkinsonian) |
Supportive features (Commonly present in DLB but not proven to have diagnostic specificity) | |||
Repeated falls and syncope | Yes | No | Yes |
Transient loss of consciousness | Yes | No | No |
Severe autonomic dysfunction | Yes | No | No |
Hallucinations in other modalities | Yes | No | No |
Systematized delusions | Yes | No | Yes |
Depression | Yes | Yes | Yes |
Relative preservation of medial temporal lobe structures on MRI | Yes | Yes | Yes |
Generalized low uptake on PET perfusion scan with reduced occipital activity | Yes | No | Extensive hypometabolism |
Prominent slow wave activity on EEG with temporal lobe transient sharp waves | Yes | No (biphasic and triphasic periodic complex) | Slow but without temporal lobe transient sharp waves |
Other | |||
Mean age of onset (years) | 75 | 70 | 42 |
Mean duration (years) | 7 | 0.5 | 5 |
Detection of 14.3.3 protein | Rarely (3 cases reported) | Yes | Yes |