Sarah Al-Bachari

Arterial spin labelling reveals prolonged arterial arrival time in idiopathic Parkinson's disease.

Idiopathic Parkinsons disease (IPD) is the second most common neurodegenerative disease, yet effective disease modifying treatments are still lacking. Neurodegeneration involves multiple interacting pathological pathways. The extent to which neurovascular mechanisms are involved is not well defined in IPD. We aimed to determine whether novel magnetic resonance imaging (MRI) techniques, including arterial spin labelling (ASL) quantification of cerebral perfusion, can reveal altered neurovascular status (NVS) in IPD. Fourteen participants with IPD (mean ± SD age 65.1 ± 5.9 years) and 14 age and cardiovascular risk factor matched control participants (mean ± SD age 64.6 ± 4.2 years) underwent a 3T MRI scan protocol. ASL images were collected before, during and after a 6 minute hypercapnic challenge. FLAIR images were used to determine white matter lesion score. Quantitative images of cerebral blood flow (CBF) and arterial arrival time (AAT) were calculated from the ASL data both at rest and during hypercapnia. Cerebrovascular reactivity (CVR) images were calculated, depicting the change in CBF and AAT relative to the change in end-tidal CO2. A significant (p = 0.005) increase in whole brain averaged baseline AAT was observed in IPD participants (mean ± SD age 1532 ± 138 ms) compared to controls (mean ± SD age 1335 ± 165 ms). Voxel-wise analysis revealed this to be widespread across the brain. However, there were no statistically significant differences in white matter lesion score, CBF, or CVR between patients and controls. Regional CBF, but not AAT, in the IPD group was found to correlate positively with Montreal cognitive assessment (MoCA) scores. These findings provide further evidence of alterations in NVS in IPD.

Late Onset Epilepsy and Occult Cerebrovascular Disease

The interface between cerebrovascular disease (CVD) and epilepsy is complex and multifaceted. Late-onset epilepsy (LOE) is increasingly common and is often attributed to CVD, and is indeed associated with an increased risk of stroke. This relationship is easily recognizable where there is a history of stroke, particularly involving the cerebral cortex. However, the relationship with otherwise occult, subcortical CVD is currently less well established yet causality is often invoked. In this review, we consider the diagnosis of LOE in clinical practice—including its behaviour as a potential mimic of acute ischemic stroke and transient ischemic attack; evidence for an association between occult CVD and LOE; and potential mechanisms of epileptogenesis in occult CVD, including potential interrelationships between disordered cerebral metabolism and perfusion, disrupted neurovascular unit integrity, blood–brain barrier dysfunction, and inflammation. We also discuss recently recognized issues concerning antiepileptic drug treatment and vascular risk and consider a variety of less common CVD entities associated with seizures.

Structural and physiological MRI correlates of occult cerebrovascular disease in late-onset epilepsy

Late-onset epilepsy (LOE), with onset after 50 years of age, is often attributed to underlying occult cerebrovascular disease. LOE is associated with a three-fold increase in subsequent stroke risk, therefore it is important to improve our understanding of pathophysiology. In this exploratory study, we aimed to determine whether established structural magnetic resonance imaging markers and novel physiological imaging markers of occult cerebrovascular disease were more common in patients with LOE than age-matched controls. Sixteen patients with LOE (mean age ± SD: 67.6 ± 6.5 years) and 15 age-matched control subjects (mean age: 65.1 ± 3.9 years) underwent a 3 T MRI scan protocol. T1-weighted images and T2-weighted fluid attenuated inversion recovery (FLAIR) images were used to determine cortical grey matter volume and white matter hyperintensity (WMH) volume respectively, whilst multiple delay time arterial spin labelling (ASL) images were collected at rest and during a hypercapnic challenge. Cerebral blood flow (CBF) and arterial arrival time (AAT) were calculated from ASL data under both normocapnic and hypercapnic conditions. Cerebrovascular reactivity was also calculated for both CBF and AAT relative to the change in end-tidal CO2. Patients with LOE were found to have significantly lower cortical volume than control subjects (33.8 ± 3.8% of intracranial volume vs. 38.0 ± 5.5%, p = 0.02) and significantly higher WMH volume (1339 ± 1408 mm3 vs. 514 ± 481 mm3, p = 0.047). Baseline whole brain AAT was found to be significantly prolonged in patients with LOE in comparison to control subjects (1539 ± 129 ms vs. 1363 ± 167 ms, p = 0.005). Voxel-based analysis showed the significant prolongation of AAT to be predominantly distributed in the frontal and temporal lobes. Voxel-based morphometry showed the lower cortical volume to be localised primarily to temporal lobes. No significant differences in CBF or cerebrovascular reactivity were found between the two groups. Baseline whole brain AAT and cortical volume differences persisted upon further analysis to take account of differences in smoking history between patients and control subjects. These findings suggest that occult cerebrovascular disease is relevant to the pathophysiology of LOE.

Structural and physiological neurovascular changes in idiopathic Parkinson's disease and its clinical phenotypes.

Neurovascular changes are likely to interact importantly with the neurodegenerative process in idiopathic Parkinson’s disease (IPD). Markers of neurovascular status (NVS) include white matter lesion (WML) burden and arterial spin labelling (ASL) measurements of cerebral blood flow (CBF) and arterial arrival time (AAT). We investigated NVS in IPD, including an analysis of IPD clinical phenotypes, by comparison with two control groups, one with a history of clinical cerebrovascular disease (CVD) (control positive, CP) and one without CVD (control negative, CN). Fifty-one patients with IPD (mean age 69.0 ± 7.7 years) (21 tremor dominant (TD), 24 postural instability and gait disorder (PIGD) and six intermediates), 18 CP (mean age 70.1 ± 8.0 years) and 34 CN subjects (mean age 67.4 ± 7.6 years) completed a 3T MRI scan protocol including T2-weighted fluid-attenuated inversion recovery (FLAIR) and ASL. IPD patients showed diffuse regions of significantly prolonged AAT, small regions of lower CBF and greater WML burden by comparison with CN subjects. TD patients showed lower WML volume by comparison with PIGD patients. These imaging data thus show altered NVS in IPD, with some evidence for IPD phenotype-specific differences.

Extracranial arterial wall volume is increased and shows relationships with vascular MRI measures in idiopathic Parkinson’s disease

OBJECTIVE Idiopathic Parkinsons disease (IPD) is the second most common neurodegenerative disorder, often complicated by dementia. Cardiovascular risk factors and spontaneous cerebral emboli (SCE) are strongly associated with Alzheimers (AD) and vascular dementia (VaD). We measured SCE in the middle cerebral artery and arterial wall volume in the extracranial arteries in patients with IPD and controls, and explored the relationships with structural and physiological MRI brain neurovascular measures. PATIENTS AND METHODS Arterial wall volume over 2cm of the axillary and internal carotid arteries (ICA) bilaterally was measured by 3-D tomographic ultrasound in 15 IPD patients and 16 age/gender matched controls. SCE were counted by Transcranial Doppler (TCD) using international consensus criteria. Venous to arterial circulation shunting (v-aCS), usually through a patent foramen ovale (PFO), was measured using a TCD technique with intravenous microbubble contrast. Structural and physiological MRI brain neurovascular measures, acquired separately, comprised white matter lesion volume (WMLV), cerebral blood flow (CBF) and arterial arrival time (AAT). RESULTS Mean (95% CI) axillary and ICA wall volume was higher in IPD patients at 523 mm3 (446, 600) and 455 mm3 (374, 536) respectively compared with 412 mm3 (342, 483) and 408 mm3 (362, 454) in controls being significant for the axillary artery (p = 0.04). Cerebral WMLV was related to mean arterial wall volume for both axillary (r = 0.555, p = 0.009) and ICA (r = 0.559, p = 0.026) in all participants. SCE were detected in four IPD patients and three controls (p = 1.00). Two IPD patients and three controls were positive for a v-aCS equivalent to PFO (p = 0.477). CONCLUSION Although frequent in AD and VaD, neither SCE nor v-aCS were associated with IPD. This is the first study to demonstrate arterial wall volume is increased in IPD and relates to WMLV.

PO071 Mri assessment of neurovascular changes in idiopathic parkinson’s disease

The extent to which neurovascular mechanisms are involved in Idiopathic Parkinson’s disease (IPD) is not well defined, but is important because this might open up new therapeutic approaches. We have investigated neurovascular status (NVS) in IPD using novel MRI techniques. Fifty-one patients with IPD (mean age 69.0±7.7 years) (21 tremor dominant, 24 postural instability and gait disorder and 6 intermediates) were compared with 18 control positive (CP) subjects with a history of clinical cerebrovascular disease (mean age 70.1±8.0 years) and 34 control negative (CN) subjects without a history of cerebrovascular disease (mean age 67.4±7.6 years). Each underwent a 3 T MRI protocol including arterial spin labelling measurements of cerebral blood flow (CBF) and arterial arrival time (AAT) and dynamic contrast enhanced measures of blood-brain barrier integrity. IPD subjects showed diffuse regions of significantly prolonged AAT and focal regions of lower CBF by comparison with CN, comparable to CP subjects. IPD subjects also showed increased leakiness of the blood-brain barrier in basal ganglia regions compared to the CN group, with a similar pattern between IPD phenotypes. These data provide evidence of altered NVS in IPD.

SIMILARITIES IN ARTERIAL ARRIVAL TIME PROLONGATION AND POSTERIOR HYPOPERFUSION IN PATIENTS WITH IDIOPATHIC PARKINSON'S DISEASE AND STROKE

The relevance of impaired neurovascular function in idiopathic Parkinsons disease (IPD) is unknown. Furthermore, it is unknown whether any such changes might contribute to, or be the effect of, neurodegeneration, or potentially reflect comorbid cerebrovascular disease (CVD). MRI arterial spin labelling (ASL) is a suitable, non-invasive tool for quantifying cerebral haemodynamics including measurements of cerebral blood flow (CBF) and arterial arrival time (AAT). Prolonged AAT has been attributed to increased collateral circulation, chronic vasodilatation and/or increased tortuosity of vessels. 12 subjects with CVD (mean age 68.9±7.8), 19 tremor dominant (TD) IPD subjects (mean age 67.2±0.6), 17 postural instability and gait dominant (PIGD) IPD subjects (mean age 70.7±6.6) and 23 control subjects (mean age 65.1±5.7) completed a 3T MRI scanning protocol, including ASL. CVD subjects had significantly more cerebrovascular risk factors than the other groups. A significant widespread increase in baseline AAT was seen in IPD (both TD and PIGD) and CVD groups when compared to controls. Voxel-based analysis of CBF revealed significant focal hypoperfusion (predominantly posteriorly) in the TD, PIGD and the CVD groups when compared to controls. These novel findings suggesting similar alterations in cerebral haemodynamics in IPD and CVD groups merit further study.

CLINICAL AND ELECTROPHYSIOLOGICAL CHARACTERISTICS OF 103 PATIENTS WITH SENSORY NEURONOPATHY

Sensory Neuronopathy (SN) represents a distinct peripheral nervous system disorder associated with degeneration of the Dorsal Root Ganglia. We present our retrospective review of 103 patients with an electro-clinical diagnosis of SN. Average age of onset was 54 yr. Aetiologies included Sjogrens (21%), Probable Inflammatory (16%), Idiopathic (29%), Inherited (20%), Toxic (5%) and paraneoplastic (9%). Of those with inherited SN (n=21); CANVAS syndrome 2/21, mitochrondrial cytopathy 9/21 with 4 confirmed POLG1 mutations, 3/21 presumed HSANIIb, Frederichs Ataxia 1/21 and 6/21 unidentified phenotypes. Clinically, acquired causes commonly presented with pain (62%), asymmetrical/non-length dependent sensory disturbance (91%) as compared to the inherited group who are more likely to present with gait disturbance without prominent sensory symptoms (52%). Of the cohort with presumed inflammatory disease, 29 patients were immunosuppressed with 12 patients responding to a combination of steroids and Mycophenolate. IVIG was not found to be beneficial with no sustained benefit in 7 patients. Paraneoplastic causes (n=9) included Breast (n=2), Neuroendocrine tumours (n=2), Carcinoid (n=2), Bowel (n=1), SCLC (n=1) and unknown primary (n=1) with only 4 Hu positive Conclusions Sensory neuronopathy is clinically and aetiologically pleomorphic. In cases with a suspected inflammatory cause it is worthwhile considering a trial of immunomodulatory treatment.