Iatrogenic cerebral amyloid angiopathy in older adults.

BACKGROUND AND PURPOSE: An increasing number of cases of iatrogenic cerebral amyloid angiopathy (CAA) have now been reported worldwide. Proposed diagnostic criteria require a history of medical intervention with potential for amyloid-ß transmission, for example those using cadaveric dura mater or requiring instrumentation of the brain or spinal cord. Clinical presentation occurs after an appropriate latency (usually three or four decades); to date, most patients with iatrogenic CAA have had 'early-onset' disease (compared to sporadic, age-related, CAA), as a consequence of childhood procedures. RESULTS: We describe five cases of possible iatrogenic CAA in adults presenting in later life (aged 65 years and older); all had prior neurosurgical interventions and presented after a latency suggestive of iatrogenic disease (range 30-39 years). Use of cadaveric dura mater was confirmed in one case, and highly likely in the remainder. CONCLUSION: The presentation of iatrogenic CAA in older adults widens the known potential spectrum of this disease and highlights the difficulties of making the diagnosis in this age group, and particularly in differentiating iatrogenic from sporadic CAA. Increased vigilance for cases presenting at an older age is essential for furthering our understanding of the clinical phenotype and broader implications of iatrogenic CAA.

Underestimation of cognitive impairments by the Montreal Cognitive Assessment (MoCA) in an acute stroke unit population.

BACKGROUND AND PURPOSE: The Montreal Cognitive Assessment (MoCA) is an increasingly popular clinical screening tool for detecting cognitive impairment in stroke, but few studies have directly compared performance on the MoCA with neuropsychological assessment. Our retrospective study examined the extent to which intact performance on the MoCA reflects intact cognition as determined by neuropsychological assessment. METHODS: In this retrospective study, cognitive profiles for 136 acute stroke patients admitted to the Acute Stroke Unit who had available MoCA and neuropsychological assessment data were examined. RESULTS: 22% of our patients were deemed cognitively intact on the MoCA. Of these, 78% were found to be impaired (≤ 5%ile) on neuropsychological assessment in one or more cognitive domains. The most common impairments were in general intelligence, information processing speed and visual memory; three areas not assessed by the MoCA. In addition, a high proportion (up to 59%) of patients who scored the maximum points in one of the MoCA-specified domains were impaired on comparable neuropsychological assessment. CONCLUSIONS: Our findings suggest that although the MoCA may be a useful screening tool post-stroke in detecting gross impairments, neuropsychological assessment is still necessary for a comprehensive and reliable detection of domain-specific cognitive deficits, which can more reliably inform us for realistic goal setting and vocational advice vital for effective rehabilitation.

Opposing roles of sensory and parietal cortices in awareness in a bistable motion illusion.

Motion-induced blindness (MIB) is a bistable visual phenomenon in which stationary disks surrounded by a moving pattern intermittently disappear from the viewer's awareness. We explored the cortical network that subserves the MIB phenomenon by targeting its constituent parts with disruptive transcranial magnetic stimulation (TMS), in the form of continuous theta burst stimulation (cTBS). Previous neuroimaging and TMS studies have implicated the right posterior parietal cortex (rPPC) in perceptual transitions such as binocular rivalry, while the visual area V5/MT has been suggested to play a key role in MIB. In this study, we found that cTBS applied to the rPPC lengthened the duration of disappearance in MIB, while cTBS applied to V5/MT shortened the duration of disappearance and decreased the frequency of disappearance in MIB. These results demonstrate a causal role for both the rPPC and V5/MT in MIB, and suggest that the rPPC is involved in shifting resources between competing functional areas, while V5/MT processing initiates and maintains MIB.

Theta burst stimulation in the rehabilitation of the upper limb: a semirandomized, placebo-controlled trial in chronic stroke patients.

BACKGROUND: Noninvasive cortical stimulation could represent an add-on treatment to enhance motor recovery after stroke. However, its clinical value, including anticipated size and duration of the treatment effects, remains largely unknown. OBJECTIVE: The authors designed a small semi-randomized clinical trial to explore whether long-lasting clinically important gains can be achieved by adding theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (TMS), to a rehabilitation program for the hand. METHODS: A total of 41 chronic stroke patients received excitatory TBS to the ipsilesional hemisphere or inhibitory TBS to the contralesional hemisphere in 2 centers; each active group was compared with a group receiving sham TBS. TBS was followed by physical therapy for 10 working days. Patients and therapists were blinded to the type of TBS. Primary outcome measures (9-hole Peg Test [9HPT], Jebsen Taylor Test [JTT], and grip and pinch-grip dynamometry) were assessed 4, 30, and 90 days post treatment. The clinically important difference was defined as 10% of the maximum score. RESULTS: There were no differences between the active treatment and sham groups in any of the outcome measures. All patients achieved small sustainable improvements--9HPT, 5% of maximum (confidence interval [CI] = 3%-7%); JTT, 5.7% (CI = 3%-8%); and grip strength, 6% (CI = 2%-10%)--all below the defined clinically important level. CONCLUSIONS: Cortical stimulation did not augment the gains from a late rehabilitation program. The effect size anticipated by the authors was overestimated. These results can improve the design of future work on therapeutic uses of TMS.

The role of the cerebellum in 'real' and 'imaginary' line bisection explored with 1-Hz repetitive transcranial magnetic stimulation.

The role of the cerebellum is well characterized for many motor processes and for some cognitive tasks, although its contribution to lateralized spatial judgement has never been probed directly. To address this omission, we investigated the effects of cerebellar disruption on two different line bisection tasks in eight healthy subjects. Based on previous evidence of crossed cerebellar-cortical connections we predicted a shift in the perceived midline that would occur in opposite directions depending on the cerebellar hemisphere targeted. Repetitive transcranial magnetic stimulation (rTMS), given at 1-Hz (600 pulses), was used as a non-invasive way to interfere with processing in the cerebellar cortex. Performance was assessed for both 'physical' line bisection using a newly developed Landmark variant task and for 'mental' line bisection using number pairs. The effects for number line bisection were lateralized--left but not right cerebellar rTMS increased rightward errors, whereas for physical line bisection rTMS to either hemisphere did not affect performance. Effects due to neck muscle contraction and changes in eye position were ruled out with appropriate control stimulation sites, and eye-tracking. The results confirm the role of the cerebellum in spatial judgement, and, for the first time, demonstrate direct cerebellar involvement in the generation of the midline in 'imaginal' (number) space. The difference between number line and physical line bisection effects is discussed with reference to pre-existing models of cerebellar hemispheric specialization and functional topography.

'Noisy patients'--can signal detection theory help?

Signal detection theory tests an observer's ability to discriminate between signal and noise. Deciding whether or not a patient's symptoms warrant further investigation or treatment is an example of this task in the clinical setting. Noise can exist within the observer--for example, in the brain of a tired or inexperienced doctor--or can arise from an external source such as the patient. Patients can produce external noise by giving numerous unrelated presenting complaints, providing overly detailed accounts of their symptoms, or simply talking too quickly. The more noise that is present, the harder the signal (such as a new disease or a notable change in an old condition) is to detect. Patients in the neurology clinic seem to be 'noisier' than average, perhaps owing to the long duration of their condition in many cases and the relatively high proportion of patients with medically unexplained symptoms. The ability to interpret such 'noisy' histories often underpins the neurological diagnosis. This Review aims to promote the relevance of signal detection theory to the overworked neurologist on the ward or in the clinic and explores strategies to reduce the noise generated both within the brain of the doctor and by patients.