A 56-year-old woman consulted an ophthalmologist because of progressive vision loss. Visual acuity, color vision, funduscopy, electroretinography, and visual evoked potentials were normal. There was a bilateral visual field constriction, but reliability indices were poor. No specific diagnosis was made, and nonorganic visual field loss was a diagnostic consideration. Two years later, she complained of memory loss and disorientation that was attributed to depression. Brain CT showed diffuse cortical atrophy.
The patient was referred to a neurologist, and neuropsychological evaluation detected frontal dysfunction, apraxia, and apperceptive agnosia. Throughout the following year, she developed memory loss, aphasia, severe depression, anxiety, irritability, and aggressiveness, and she received several antidepressants. SPECT revealed right hemisphere hypoperfusion with the absence of activity in the right parietotemporal region. The following year, she experienced visual hallucinations and cognitive fluctuations. She did not improve with donepezil, and in the last months of her life, there was progressive impairment of memory and orientation, apraxia, aphasia, agnosia, mood disorder, and clinophilia. Neurological examination revealed global rigidity, hypomimia, bradykinesia, and parkinsonian gait. The patient did not use her left hand and required nasoduodenal feeding due to severe dysphagia and buccolingual apraxia. PET showed bilateral parieto-occipital hypometabolism, while MRI revealed temporoparieto-occipital atrophy predominantly on the right. With the onset of cortical visual signs and progression to global dementia, she was diagnosed with PCA and progression to presenile AD. She died of respiratory infection, and neuropathology revealed AD (Braak stage VI) with numerous plaques and tangles predominantly in cortical areas, including primary visual cortex, with the absence of alpha-synuclein.
Our patients presented with complex visual symptoms in the absence of ocular pathology. The diagnosis of PCA was made 1–5 years after the onset of symptoms and established by the presence of visual cortical complaints, clinical evolution, and neuroimaging findings, fulfilling many of the clinical criteria proposed by Tang-Wai et al (4) (Table 1). The presenting visual complaints were nonspecific, and as in other case series (4,5), patients initially presented to an ophthalmologist. Unlike typical AD, memory, insight, and judgment were relatively preserved until late in the course, resulting in the failure to recognize PCA. This diagnostic delay has been reported to range between 1 and 9 years (4,5). The differential diagnosis includes Lewy body dementia (LBD), Creutzfeldt-Jakob disease (Heidenhain variant), cerebrovascular disease, and nonorganic visual loss.
The mean age of onset of PCA is earlier than in classical AD (4,5). Onset between 40 and 85 years has been reported, but most cases start between 50 and 60 years (4–7). Almost all cases are sporadic. Some have a familial history of late-onset dementia (5,7) but not of PCA, with the exception of 2 sisters reported by Otsuki et al (8). Our patients had onset ages between 50 and 66 years, and none had a family history of AD.
The spectrum of clinical signs of PCA reflects dysfunction of the dorsal (occipito-parietal) and/or the ventral (occipitotemporal) visual streams or primary visual cortical dysfunction (4,9). Almost a quarter of the patients with PCA develop visual hallucinations (4–6), and some have LBD at autopsy. In case 4, despite the presence of hallucinations and spontaneous parkinsonism, the neuropathological diagnosis was AD.
Approximately half of the patients with PCA eventually complain of intermittent memory loss (6), but this is never a prominent initial feature. In most cases, memory loss develops later in the course of the disease. In neuropsychological studies, PCA patients are significantly more impaired in visual perception, spatial memory, visual attention, and visuospatial reasoning compared to AD patients, who are more impaired in episodic memory (9).
Hemianopic visual field loss is thought to be underdiagnosed (10), probably because visual fields are either tested only by confrontation techniques or perimetric examination is not fully reliable because of attention deficits and apraxia of PCA patients.
MRI typically shows bilateral PCA, predominantly affecting the occipital, parietal, and temporal lobes (11). If MRI appears normal or reveals nonspecific atrophy, voxel-based morphometry studies show a pattern of posterior lobe atrophy compared to controls (7). Cortical atrophy is bilateral but more severe on the right side. In studies comparing patients with PCA to those with typical AD, there is greater atrophy in the right visual association cortex and less in the left hippocampus (11). PET studies also show greater parieto-occipital impairment, also with right predominance (Fig. 5) (12). Frontal lobe involvement, although typical of AD, has been reported in PCA, clinically and with functional neuroimaging. This may be because of the degeneration of the afferent input from the parietal-occipital cortices contributing to ocular apraxia (11,12).
Autopsy findings of PCA patients usually show AD-type pathology but of posterior distribution and with hippocampal preservation (4). More rarely, some cases have shown LBD. PCA is a clinical syndrome and may be considered as a rare focal onset variant of AD or LBD, or alternatively regarded as a distinct entity.
No treatments for PCA have been evaluated in clinical trials. Cholinesterase inhibitors are sometimes used, but their effectiveness is unproven.
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© 2012 Lippincott Williams & Wilkins, Inc.
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