Is cerebral autoregulation impaired in Parkinson's disease? A transcranial Doppler study

Orthostatic hypotension (OH) is one of the many autonomic disturbances observed in Parkinson's disease (PD). It has been debated whether an additional impairment of cerebral autoregulation (CA) in PD patients may exacerbate the consequences of OH upon brain perfusion. We assessed CA in PD patients and the potential influence of dopaminergic agents. CA was determined by means of transcranial Doppler (TCD) monitoring of the middle cerebral artery (MCA) at rest and during a thigh cuff release test inducing a systemic blood pressure (BP) drop. Fourteen patients were investigated when taking their usual dopaminergic medication and after drug discontinuation for 12 h. A control group was composed of 11 age-matched subjects (CS). In comparison with PD patients, CS presented a significantly higher increase of the mean cerebral blood flow velocities in the MCA after the BP drop. Mean velocities were increased above the initial values in all CS, whereas a flattened curve was observed in PD patients. No significant differences could be further observed between the PD patients regarding the BP, the cerebrovascular resistance, the heart rate and the pulsatility index. These results provide evidence of an impaired cerebral autoregulation in PD patients which appears independent of dopaminergic treatment.     

Pathology of small cerebral arteries demonstrated by MRI: a marker of aging?

Brain magnetic resonance imaging frequently identifies signal abnormalities in the white matter and cerebral cortex in the elderly. They are related to a degenerative disease of the small vessels that may be of ischemic (leukoaraiosis, lacunae and infarct) or hemorrhagic (microbleeds and hematomas) origin. These lesions are part of the aging process, and compounded by vascular risk factors. They increase the occurrence frequency and severity of ischemic or hemorrhagic stroke. Their importance is also associated with the presence of cognitive and/or affective symptoms, and their impact on the occurrence and evolution of dementia remains to be evaluated. The visible consequences of this microangiopathy on MRI probably represent the focal mark of a widespread cerebrovascular disease in the brain parenchyma.     

Monitoring cerebral autoregulation after head injury. Which component of transcranial Doppler flow velocity is optimal?

Background

Cerebral autoregulation assessed using transcranial Doppler (TCD) mean flow velocity (FV) in response to various physiological challenges is predictive of outcome after traumatic brain injury (TBI). Systolic and diastolic FV have been explored in other diseases. This study aims to evaluate the systolic, mean and diastolic FV for monitoring autoregulation and predicting outcome after TBI.

Methods

300 head-injured patients with blood pressure (ABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), and FV recordings were studied. Autoregulation was calculated as a correlation of slow changes in diastolic, mean and systolic components of FV with CPP (Dx, Mx, Sx, respectively) and ABP (Dxa, Mxa, Sxa, respectively) from 30 consecutive 10?s averaged values. The relationship with age, severity of injury, and dichotomized 6?months outcome was examined.

Results

Association with outcome was significant for Mx and Sx. For favorable/unfavorable and death/survival outcomes Sx showed the strongest association (F?=?20.11; P?=?0.00001 and F?=?13.10; P?=?0.0003, respectively). Similarly, indices derived from ABP demonstrated the highest discriminatory value when systolic FV was used (F?=?12.49; P?=?0.0005 and F?=?5.32; P?=?0.02, respectively). Indices derived from diastolic FV demonstrated significant differences (when calculated using CPP) only when comparing between fatal and non-fatal outcome.

Conclusions

Systolic flow indices (Sx and Sxa) demonstrated a stronger association with outcome than the mean flow indices (Mx and Mxa), irrespective of whether CPP or ABP was used for calculation.     

Eye tracking technology: A fresh approach in delirium assessment?

The objective of this paper is to highlight the potential role of eye tracking technology (ETT) in the assessment of delirious patients. Delirium occurs in one in five general hospital admissions (Siddiqi, 2006) and its frequency will increase as society gets older. Despite its frequency and significant independent impact upon morbidity and mortality, delirium remains under studied and is frequently missed, detected late, or misdiagnosed (Farrell & Ganzani, 1995; Inouye, 2001; Kakuma, 2003). Detection is a key target for both clinical and research efforts. Assessment of attention is key to diagnosing delirium, yet nurses and non-research medical staff often fail to correctly identify inattention (Inouye et al., ; Lemiengre et al., ; Ryan et al., 2008). Eye tracking measures have been used in a plethora of key areas of psychiatric research (Crawford et al., ; Corden, Chilvers, & Skuse, 2008; Hardin, Schroth, Pine, & Ernst, 2007; Holzman, Leonard, Proctor, & Hughes, 1973), and provide an accurate and non-invasive method in the assessment of cognitive function. The potential of ETT for direct clinical applications in the assessment of attention and comprehension, key cognitive symptoms of delirium, are promising. This paper considers potential new approaches which recent advancements in non-invasive ETT may bring to the examination and understanding of delirium.     

Nighttime fears of preschool children: A potential disposition marker for anxiety?

Objective

To examine if children who suffer from significant Nighttime Fears (NF) experience higher degree of general fears and behavioral problems and to explore whether effortful control mediates NF association with internalizing problems.

Methods

One-hundred and nine preschool children (64 boys) between the ages 4 and 6 years suffering from significant NF and 30 healthy children (16 boys) were evaluated using parental reports of behavioral problems [Child Behavior Checklist (CBCL)], parental and child report of fears [Fear Survey Revised for Parents (FSS-PC), Koala Fear Questionnaire (KFQ)], and a measure of effortful control derived from the Child Behavior Questionnaire (CBQ).

Results

Children with severe NF also suffer from an increased level of a wide variety of fears other than NF, and exhibit more behavioral problems than controls both on parental and children’s measures of general fears, and main CBCL scale scores (Internalizing, Externalizing, Total score). Additionally, children with NF had lower abilities of effortful control (as manifested in CBQ attention and inhibitory control scales). Attention control mediated NF association to internalizing problems scale.

Conclusions

NF may serve as a marker for anxiety vulnerability, and this vulnerability might be mediated by abnormal attentional control. Our finding also highlights the need for a more comprehensive assessment of behavioral problems, fears and anxiety phenomena among children referred with NF.     

Cerebrospinal fluid markers of neuroinflammation in delirium: A role for interleukin-1β in delirium after hip fracture

Objective

Exaggerated central nervous system (CNS) inflammatory responses to peripheral stressors may be implicated in delirium. This study hypothesised that the IL-1β family is involved in delirium, predicting increased levels of interleukin-1β (IL-1β) and decreased IL-1 receptor antagonist (IL-1ra) in the cerebrospinal fluid (CSF) of elderly patients with acute hip fracture. We also hypothesised that Glial Fibrillary Acidic Protein (GFAP) and interferon-γ (IFN-γ) would be increased, and insulin-like growth factor 1 (IGF-1) would be decreased.

Methods

Participants with acute hip fracture aged > 60 (N = 43) were assessed for delirium before and 3–4 days after surgery. CSF samples were taken at induction of spinal anaesthesia. Enzyme-linked immunosorbent assays (ELISA) were used for protein concentrations.

Results

Prevalent delirium was diagnosed in eight patients and incident delirium in 17 patients. CSF IL-1β was higher in patients with incident delirium compared to never delirium (incident delirium 1.74 pg/ml (1.02–1.74) vs. prevalent 0.84 pg/ml (0.49–1.57) vs. never 0.66 pg/ml (0–1.02), Kruskal–Wallis p = 0.03). CSF:serum IL-1β ratios were higher in delirious than non-delirious patients. CSF IL-1ra was higher in prevalent delirium compared to incident delirium (prevalent delirium 70.75 pg/ml (65.63–73.01) vs. incident 31.06 pg/ml (28.12–35.15) vs. never 33.98 pg/ml (28.71–43.28), Kruskal–Wallis p = 0.04). GFAP was not increased in delirium. IFN-γ and IGF-1 were below the detection limit in CSF.

Conclusion

This study provides novel evidence of CNS inflammation involving the IL-1β family in delirium and suggests a rise in CSF IL-1β early in delirium pathogenesis. Future larger CSF studies should examine the role of CNS inflammation in delirium and its sequelae.     

Speech acoustic markers of early stage and prodromal Huntington's disease: A marker of disease onset?

Speech disturbances (e.g., altered prosody) have been described in symptomatic Huntington's Disease (HD) individuals, however, the extent to which speech changes in gene positive pre-manifest (PreHD) individuals is largely unknown. The speech of individuals carrying the mutant HTT gene is a behavioural/motor/cognitive marker demonstrating some potential as an objective indicator of early HD onset and disease progression. Speech samples were acquired from 30 individuals carrying the mutant HTT gene (13 PreHD, 17 early stage HD) and 15 matched controls. Participants read a passage, produced a monologue and said the days of the week. Data were analysed acoustically for measures of timing, frequency and intensity. There was a clear effect of group across most acoustic measures, so that speech performance differed in-line with disease progression. Comparisons across groups revealed significant differences between the control and the early stage HD group on measures of timing (e.g., speech rate). Participants carrying the mutant HTT gene presented with slower rates of speech, took longer to say words and produced greater silences between and within words compared to healthy controls. Importantly, speech rate showed a significant correlation to burden of disease scores. The speech of early stage HD differed significantly from controls. The speech of PreHD, although not reaching significance, tended to lie between the performance of controls and early stage HD. This suggests that changes in speech production appear to be developing prior to diagnosis.     

The WAIS-R profile as a cognitive marker of Alzheimer's disease: A misguided venture?

Abstract

The utility of a pattern on WAIS-R subtest performance (Fuld profile) in differentiating between dementia of the Alzheimer's type (DAT) and multi-infarct dementia (MID) was investigated. The Fuld profile was neither sensitive nor specific to DAT, as similar numbers of DAT subjects (15%) and MID subjects (12%) obtained a positive profile. No relationship between presence of the profile and level of education was detected. However, a positive profile in DAT subjects was associated with less severe neuropsychological impairment. Implications of this finding as well as the value of searching for a cognitive marker for DAT are discussed.     

High-dose intravenous immunoglobulin treatment and cerebral vasospasm: A possible mechanism of ischemic encephalopathy?

A 46-year-old woman with a severe polyradiculoneuropathy treated with high-dose intravenous immunoglobulin (IVIg) presented an encephalopathy with increased blood flow velocities of the middle cerebral arteries (MCAs) detected by transcranial Doppler (TCD) studies. The similitude between this observation and another case recently reported of a patient suffering from Guillain-Barré syndrome (GBS) and cerebral blood flow abnormalities after IVIg treatment prompted us to investigate the responsibility of the IVIg therapy in the genesis of these blood flow alterations. We studied therefore by TCD 10 consecutive patients who underwent this treatment for different reasons. In 1 case we observed an asymptomatic, spontaneously reversible increase in the blood flow velocities of the MCAs consistent with a vasospasm and occurring 3-10 days after completion of the therapy. Stroke and ischemic encephalopathy have been reported as possible complications of IVIg treatment. In the case under discussion, clinical events appeared shortly after the administration of the IVIg therapy and responded favorably to a treatment with nimodipine. Other etiopathogenic mechanisms, in particular a CNS vasculopathic process related to the GBS itself, have to be considered as well. Further studies, with a larger number of patients, are therefore needed to evaluate the underlying mechanisms of blood flow abnormalities occurring sometimes in GBS patients after IVIg treatment.     

Multiple acute stroke syndrome: marker of embolic disease?

OBJECTIVE: To determine the frequency and etiologic significance of multiple acute ischemic lesions in stroke. BACKGROUND: Although patients may have more than one stroke during the course of their lives, acute ischemic stroke is usually thought of as a single event. Using diffusion-weighted imaging (DWI), an MRI technique that detects ischemic injury within minutes after onset, we have often observed multiple acute ischemic lesions. Methods: The MRI scans of 59 consecutively studied patients were reviewed to determine the frequency and etiologic significance of multiple acute ischemic lesions on DWI. RESULTS: Multiple acute ischemic lesions were present in 10 (17%) of 59 patients. The lesions usually occurred within one major circulation (anterior or posterior), but in two patients (3%), lesions occurred in both cerebral hemispheres or in the anterior and the posterior circulations. The lesions often were small and resulted from presumed multiple emboli or the break-up of an embolus. Two patients had internal carotid artery occlusive disease and four had a cardiac or aortic source. In the other four patients the source was not determined. Lesions larger than 1 cm in diameter progressed to infarction, but some smaller lesions were not seen on follow-up T2-weighted imaging. CONCLUSIONS: Multiple acute stroke lesions on DWI are common and could be caused by multiple emboli or the breakup of an embolus. In some cases it might become possible to make early inferences concerning the stroke mechanism that could be of use for immediately directing the clinical work-up and treatment of the patient.     

Focused high-resolution sonography of the suprascapular nerve: A simple surrogate marker for neuralgic amyotrophy?

Objectives

To define the diagnostic value of high-resolution ultrasound (HRUS) of the suprascapular nerve (SSN) in the diagnosis of neuralgic amyotrophy (NA).

Delirium phenomenology: what can we learn from the symptoms of delirium?

OBJECTIVES: This review focuses on phenomenological studies of delirium, including subsyndromal and prodromal concepts, and their relevance to other elements of clinical profile. METHODS: A Medline search using the keywords delirium, phenomenology, and symptoms for new data articles published in English between 1998 and 2008 was utilized. The search was supplemented by additional material not identified by Medline but known to the authors. RESULTS: Understanding of prodromal and subsyndromal concepts is still in its infancy. The characteristic profile can differentiate delirium from other neuropsychiatric disorders. Clinical (motoric) subtyping holds potential but more consistent methods are needed. Studies are almost entirely cross-sectional in design and generally lack comprehensive symptom assessment. Multiple assessment tools are available but are oriented towards hyperactive features and few have demonstrated ability to distinguish delirium from dementia. There is insufficient evidence linking specific phenomenology with etiology, pathophysiology, management, course, and outcome. CONCLUSIONS: Despite the major advancements of the past decade in many aspects of delirium research, further phenomenological work is crucial to targeting studies of causation, pathophysiology, treatment, and prognosis. We identified eight key areas for future studies.     

A columnar-supporting mode of astroglial architecture in the cerebral cortex of adult primates?

Neuronal modular (columnar) organisation of the cerebral cortex may represent an evolutionary acquisition that could optimize communication and information processing with the least volume compromise in terms of wiring. Yet, for such columns to be functionally operative adequate isolation from neighbouring units would be required, otherwise their spatial definition could be compromised. Evidence for "cable-like" processes stemming from astroglial cells has been recently presented although their existence has been forgotten for more than a century. These processes tend to form a sort of "palisade" or "brush" whose spatial distribution appears to correlate with the distribution of apical dendrites within the supragranular cortical layers. Patterned neuronal organization in the striate cortex is associated with a patterned distribution of GFAP-IR processes, both at the cellular and cell-aggregate levels. It can be tentatively proposed that evolutionary pressures resulted, in primates, in the progressive appearance of an increased length of astroglial processes in the supragranular region which may be associated with optimization of cerebral cortex modular (columnar) organization. It is interesting that this cortical region has undergone the larger growth among mammalian species during evolution, and would bear a crucial role in corticocortical interactions.