Jane Griffith

Cerebral vasomotor reactivity testing in head injury: the link between pressure and flow

Background: It has been suggested that a moving correlation index between mean arterial blood pressure and intracranial pressure, called PRx, can be used to monitor and quantify cerebral vasomotor reactivity in patients with head injury. Objectives: To validate this index and study its relation with cerebral blood flow velocity and cerebral autoregulation; and to identify variables associated with impairment or preservation of cerebral vasomotor reactivity. Methods: The PRx was validated in a prospective study of 40 head injured patients. A PRx value of less than 0.3 indicates intact cerebral vasomotor reactivity, and a value of more than 0.3, impaired reactivity. Arterial blood pressure, intracranial pressure, mean cerebral perfusion pressure, and cerebral blood flow velocity, measured bilaterally with transcranial Doppler ultrasound, were recorded. Dynamic cerebrovascular autoregulation was measured using a moving correlation coefficient between arterial blood pressure and cerebral blood flow velocity, the Mx, for each cerebral hemisphere. All variables were compared in patients with intact and impaired cerebral vasomotor reactivity. Results: No correlation between arterial blood pressure or cerebral perfusion pressure and cerebral blood flow velocity was seen in 19 patients with intact cerebral vasomotor reactivity. In contrast, the correlation between these variables was significant in 21 patients with impaired cerebral vasomotor reactivity, whose cerebral autoregulation was reduced. There was no correlation with intracranial pressure, arterial blood pressure, cerebral perfusion pressure, or interhemispheric cerebral autoregulation differences, but the values for these indices were largely within normal limits. Conclusions: The PRx is valid for monitoring and quantifying cerebral vasomotor reactivity in patients with head injury. This intracranial pressure based index reflects changes in cerebral blood flow and cerebral autoregulatory capacity, suggesting a close link between blood flow and intracranial pressure in head injured patients. This explains why increases in arterial blood pressure and cerebral perfusion pressure may be useful for reducing intracranial pressure in selected head injured patients (those with intact cerebral vasomotor reactivity).

Cerebral autoregulation and ageing.

Little is known about the effects of ageing on cerebral autoregulation (CA). To examine the relationship between age and CA in adults, we conducted a prospective study using a non-invasive protocol without external stimuli. We studied 32 subjects, aged 23-68 years. They were assigned to a young group (28+/-5 years) and an old group (54+/-8 years). The groups were sex-matched. Transcranial Doppler ultrasonography (TCD) was used to record bilateral middle cerebral artery flow velocities (CBFV, cm/sec). Noninvasive beat-to-beat tonometric arterial blood pressure (ABP) measurement of the radial artery was used to record spontaneous blood pressure fluctuations. The Mx, an index of dynamic cerebral autoregulation (dCA), was calculated from a moving correlation between ABP and CBFV. We did not find a correlation between age and Mx. No statistically significant difference in the Mx between the groups (0.27+/-0.23, young, vs. 0.37+/-0.24, old) was demonstrated. Age does not affect dynamic cerebral autoregulation assessed by the Mx index in healthy adult subjects. This study supports findings from previous papers wherein CA was measured with protocols which require external stimuli. Further studies are needed to determine CA in subjects above 70 years of age.

Tracking motor impairments in the progression of Huntington's disease

The Unified Huntingtons Disease Rating Scale is used to characterize motor impairments and establish motor diagnosis. Little is known about the timing of diagnostic confidence level categories and the trajectory of motor impairments during the prodromal phase. Goals of this study were to estimate the timing of categories, model the prodromal trajectory of motor impairments, estimate the rate of motor impairment change by category, and provide required sample size estimates for a test of efficacy in clinical trials. In total, 1010 gene‐expanded participants from the Neurobiological Predictors of Huntingtons Disease (PREDICT‐HD) trial were analyzed. Accelerated failure time models were used to predict the timing of categories. Linear mixed effects regression was used to model the longitudinal motor trajectories. Age and length of gene expansion were incorporated into all models. The timing of categories varied significantly by gene expansion, with faster progression associated with greater expansion. For the median expansion, the third diagnostic confidence level category was estimated to have a first occurrence 1.5 years before diagnosis, and the second and first categories were estimated to occur 6.75 years and 19.75 years before diagnosis, respectively. Motor impairments displayed a nonlinear prodromal course. The motor impairment rate of change increased as the diagnostic confidence level increased, with added acceleration for higher progression scores. Motor items can detect changes in motor impairments before diagnosis. Given a sufficiently high progression score, there is evidence that the diagnostic confidence level can be used for prodromal staging. Implications for Huntingtons disease research and the planning of clinical trials of efficacy are discussed.

Unawareness of motor phenoconversion in Huntington disease

Objective: To determine whether Huntington disease (HD) mutation carriers have motor symptoms (complaints) when definite motor onset (motor phenoconversion) is diagnosed and document differences between the groups with and without unawareness of motor signs. Methods: We analyzed data from 550 HD mutation carriers participating in the multicenter PREDICT-HD Study followed through the HD prodrome. Data analysis included demographics, the Unified Huntington’s Disease Rating Scale (UHDRS) and the Participant HD History of symptoms, self-report of progression, and cognitive, behavioral, and imaging measures. Unawareness was identified when no motor symptoms were self-reported but when definite motor HD was diagnosed. Results: Of 38 (6.91%) with onset of motor HD, almost half (18/38 = 47.36%) had no motor symptoms despite signs of disease on the UHDRS motor rating and consistent with unawareness. A group with motor symptoms and signs was similar on a range of measures to the unaware group. Those with unawareness of HD signs reported less depression. Patients with symptoms had more striatal atrophy on imaging measures. Conclusions: Only half of the patients with newly diagnosed motor HD had motor symptoms. Unaware patients were less likely to be depressed. Self-report of symptoms may be inaccurate in HD at the earliest stage.

Cerebrovascular autoregulation as a neuroimaging tool

Functional transcranial Doppler (fTCD) sonography provides a high temporal resolution measure of blood flow and has over the years proved to be a valuable tool in the clinical evaluation of patients with cerebrovascular disorders. More recently, due to advances in physics and computing, it has become possible to derive indices of cerebrovascular autoregulation (CA) as well as cerebrovascular pressure reactivity (CR), using non-invasive techniques. These indices provide a dynamic representation of the brains regulatory blood flow mechanisms not only in pathological states but also in health. However, whilst the temporal resolution of these regulatory indices is very good, spatially, the localization of brain regions remains very poor, thus limiting its brain mapping capacity. Functional MRI, on the contrary, is a brain-imaging technique that operates on similar blood flow principles; however, unlike fTCD, it provides high spatial resolution. Because both fTCD and fMRI determine blood flow-dependant imaging parameters, the coupling of fTCD with fMRI may provide greater insight into brain function by virtue of the combined enhanced temporal and spatial resolution that each technique affords. This review summarizes the fTCD technique with particular emphasis on the CA and CR indices and their relationship in traumatic brain injury as well as in health.

I01 Unawareness of motor phenoconversion in huntington disease

Background Unawareness of disease manifestations in neurodegenerative diseases has been defined by Flashman et al 2002 as “pathological unawareness of a neurological or functional deficit” and by Antoine et al 2004 as “the discrepancy between the patients self report and the report of a natural caregiver or the clinical rating of a health professional”. Affected patients may have no complaints (symptoms) in contrast with a carers or examiners observations. Unawareness of movements and impairments in cognitive, emotional and functional capacity are documented in diagnosed Huntington Disease (HD). The PREDICT-HD study of mutation carriers allows a study of unawareness in the HD prodrome to phenoconversion. Aims Determine if PREDICT-HD participants have motor complaints at the time motor phenoconversion and document differences between groups with and without awareness on cognitive, functional and behavioural measures. Methods The PREDICT-HD database cross sectional information recorded at the third annual study visit for participants was reviewed. Demographics, motor, functional, cognitive and behavioural scores were analysed. Unawareness was identified as lack of agreement between participant report of symptoms and the trained examiners rating of a diagnosis of unequivocal signs of HD. The groups with and without self-reported symptoms and an examiner rating of motor onset were compared on a range of cognitive, functional and behavioural measures, accounting for CAG repeat length and age. Results Of 550 participants at the third annual PREDICT—HD visit, motor phenoconversion was recorded in 38 (6.91%). Of those, 18 (47.36 %) reported that they had no motor symptoms but were given a similar motor rating to those who reported having symptoms. The groups with and without reported motor symptoms but with signs were similar on measures of executive dysfunction and motor score. Phenoconverters without symptoms reported less depression. Conclusions Poor awareness may occur in the prodromal stage and at phenoconversion to early HD or “HD onset”, as well as in later stages. Unawareness should be considered in assessment and provision of care.