progressive course than other forms. As in other forms of prion disease, there is no known treatment and death is inevitable.

The diagnosis of sporadic CJD can be suspected on clinical grounds and is confirmed with brain biopsy, which shows a characteristic triad of spongiform change, neuronal loss and gliosis. Amyloid plaques are found in 10% of cases and immunocytochemical staining for the protease-resistant prion protein associated with the disease is uniformly present. Characteristic EEG changes consist of diffuse slowing with periodic high-amplitude biphasic or tri-phasic discharges. CSF markers such as the 14-3-3 protein, neuron-specific enolase and total Tau are also helpful in diagnosis, but are not uniformly present and may also be present in other neurologic conditions. MRI is more reliable than CSF markers in the diagnosis of CJD. Characteristic patterns of hyperintense signal abnormalities involving the cerebral cortex and basal ganglia have been described and have a greater than 90% specificity for CJD. In sporadic CJD, the caudate nucleus and putamen are typically involved, whereas variant CJD affects the pulvinar of the thalamus. Initially described on T2-weighted images, abnormal signal changes are better detected using proton density, FLAIR or diffusion-weighted MRI sequences. Although more than half of patients with CJD eventually show characteristic MRI abnormalities, early in the course of the disease routine MRI sequences are often normal.

Diagnosis: Creutzfeldt–Jakob disease (Heidenhain variant).

Non-dominant parietal lobe syndrome with negative neuro-imaging

Case: A 61-year-old chemistry professor experienced slowly progressive visual difficulty over a four-year period. Specifically, she described a tendency to lose her place on the page when reading, lecturing or playing music. She sometimes misreached for objects and would often veer to the right when driving. A general ophthalmic examina-

tion was normal except for a left homonymous inferior quadrantanopic defect (Figure 10.10). Neurologic testing showed an alert and attentive woman with fluent speech and good repetition. She was able to recall three objects at five minutes and could read fluently. She exhibited marked impairment, however, on tests of spatial organization, including difficulty copying figures, matching shapes, and filling in the numbers on a clock, along with evidence of left-sided neglect (Figure 10.11). Thyroid function tests, a serum B12 level, FTA and metabolic panel were all normal as was a brain MRI with contrast.

Can you localize this patient’s problem?

This patient displays a deficit of spatial organization, manifest as constructional apraxia and leftsided neglect, pointing to dysfunction involving the right (non-dominant) parietal lobe. Her visual field defect is also consistent with this localization. Based on her slowly progressive course and unrevealing work-up, a presumptive diagnosis of Alzheimer’s disease was made. Over the next three years she experienced further difficulty with cognitive tasks including trouble with calculations and memory deficits and was forced to retire from teaching because of these symptoms. A positron emission tomography (PET) scan performed five years after onset of symptoms showed hypometabolism in the posterior cerebral hemispheres, consistent with Alzheimer’s disease (Figure 10.12).

Discussion: Alzheimer’s disease is the most frequent dementing disorder affecting the elderly. It is characterized by insidious onset of progressive cognitive decline and by its unique pathology. While generally thought of as a diffuse dementing process, the hallmark neuropathologic findings in Alzheimer’s disease (neuritic plaques and neurofibrillary tangles) are not evenly distributed in the cortex but are rather concentrated in areas of greater neuronal vulnerability. Functional imaging studies have corroborated this regional susceptibility, demonstrating hypometabolism primarily in the

posterior parietal lobes and adjacent temporal and occipital cortex.

In keeping with the neuropathologic findings, the clinical features, especially in the early stage of disease, often manifest as selective rather than global cognitive dysfunction, such as word-finding difficulty or problems with calculations. Patients in whom the brunt of the disease affects the right posterior parietal lobe typically present with visual symptoms related to spatial disorganization, as in the above case, sometimes referred to as the “visual variant of Alzheimer’s disease”. In the later stages of the disease, when both posterior hemispheres are involved, patients have even more profound visual difficulty, including inability to attend to more than one visual stimulus at a time, termed simultanagnosia. When accompanied by “optic ataxia” (difficulty pointing to a target) and “psychic paralysis of gaze” (difficulty directing the eyes toward an object of interest) this is termed Balint’s syndrome and indicates bilateral damage to the posterior visual

association areas. Recognition of these visual presentations of Alzheimer’s disease is particularly relevant to eye care providers who are often the first to be consulted for these patients’ initial symptoms. The diagnosis in such cases may be challenging, as cognitive function is otherwise unimpaired and routine neuro-imaging is unrevealing. Functional imaging studies may be particularly helpful in this setting.

In addition to these higher cortical deficits, there are other mechanisms which may affect vision in patients with Alzheimer’s disease. There is histopathologic evidence of progressive retinal ganglion cell loss, particularly affecting M- cell pathways, which are thought to be involved in global interpretation of spatial organization based on motion and depth discrimination. In addition, patients with Alzheimer’s disease display a variety of ocular motility abnormalities including fixational instability, prolonged saccadic latency, poor tracking, and loss of saccadic velocity

Figure 10.11 Constructional testing in the above patient with symptoms of spatial disorganization. The drawings (top) on the right represent the patient’s efforts to copy the figures on the left. Below, the patient was asked to fill in the numbers as they would appear on a clock.

and accuracy, which may further impair visual function.

In this case and the preceding one, the leading edge of a dementing illness was a homonymous hemianopia. The underlying disease process in the first patient was Creutzfeld–Jacob disease and, in this patient, Alzheimer’s disease. In each case, the pathologic process was not seen on MRI, not because the lesion was too small or because it was overlooked, but because these particular degenerative processes do not generally produce visible changes on routine neuro-imaging studies. In the second patient, the pathology was eventually demonstrated with functional imaging. Although these two disorders share some common features,

Figure 10.12 Axial PET scan of the above patient shows hypometabolism in the parietal-occipital regions (arrowheads), which is more prominent on the right side (larger arrowhead). Areas with higher metabolic activity appear red, those with lowest activity are dark blue and intermediate areas are green to yellow.

the time course of each is sufficiently different to enable differentiation in most cases. Non-ketotic hyperglycemia, migraine, hypoxic encephalopathy and post-ictal states can similarly produce a homonymous hemianopia with negative neuroimaging, but the acute nature of those syndromes is distinctive and in such cases the main differential is an ischemic stroke (Table 10.5).

Table 10.5 Conditions producing cortical visual loss with negative MRI

Alzheimer’s disease

Creutzfeldt–Jakob disease

Non-ketotic hyperglycemia

Migraine

Seizures (ictal and post-ictal)

Hypoxic-ischemic encephalopathy