Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Jul 2013
Review Case ReportsDysfunction of the locus coeruleus-norepinephrine system and related circuitry in Parkinson's disease-related dementia.
Although resting tremor, cogwheel rigidity, hypokinesia/bradykinesia and postural instability usually dominate the clinical picture of sporadic Parkinson's disease (PD), both clinical and epidemiological data reveal that a wide variety of additional symptoms impair patients' quality of life considerably, parallel to the chronic progressive neurodegenerative movement disorder. Autopsy based retrospective studies have shown that α-synuclein immunoreactive Lewy pathology (LP) develops in the locus coeruleus (LC) of patients with neuropathologically confirmed sporadic PD, as well as in individuals with incidental (prodromal or premotor) Lewy body disease but not in age and gender matched controls. ⋯ The contribution of noradrenergic deficit to cognitive dysfunction in PD has been underappreciated. Noradrenergic therapeutic interventions might not only alleviate depressive symptoms and anxiety but also delay the onset of cognitive decline.
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J. Neurol. Neurosurg. Psychiatr. · Jul 2013
Pulsatility in CSF dynamics: pathophysiology of idiopathic normal pressure hydrocephalus.
It is suggested that disturbed CSF dynamics are involved in the pathophysiology of idiopathic normal pressure hydrocephalus (INPH). The pulsatility curve describes the relationship between intracranial pressure (ICP) and the amplitude of cardiac related ICP pulsations. The position of baseline ICP on the curve provides information about the physiological state of the CSF dynamic system. The objective of the study was to investigate if shunt surgery modifies the pulsatility curve and the baseline position on the curve, and how this relates to gait improvement in INPH. ⋯ The pulsatility curve was not modified by shunt surgery, while the baseline position was shifted along the curve. Observed differences between gait improvers and non-improvers support cardiac related ICP pulsations as a component of INPH pathophysiology.
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J. Neurol. Neurosurg. Psychiatr. · Jul 2013
Poststroke dementia is associated with recurrent ischaemic stroke.
To investigate whether poststroke dementia (PSD) diagnosed after ischaemic stroke predicts recurrent ischaemic stroke in long-term follow-up. ⋯ Poststroke dementia predicts recurrence of ischaemic stroke in long-term follow-up and should be considered when estimating prognosis.
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J. Neurol. Neurosurg. Psychiatr. · Jul 2013
ReviewTherapeutic strategies for tau mediated neurodegeneration.
Based on the amyloid hypothesis, controlling β-amyloid protein (Aβ) accumulation is supposed to suppress downstream pathological events, tau accumulation, neurodegeneration and cognitive decline. However, in recent clinical trials, Aβ removal or reducing Aβ production has shown limited efficacy. Moreover, while active immunisation with Aβ resulted in the clearance of Aβ, it did not prevent tau pathology or neurodegeneration. ⋯ Therefore, it is timely and very important to develop tau directed therapies. The pathomechanisms of tau mediated neurodegeneration are unclear but hyperphosphorylation, oligomerisation, fibrillisation and propagation of tau pathology have been proposed as the likely pathological processes that induce loss of function or gain of toxic function of tau, causing neurodegeneration. Here we review the strategies for tau directed treatments based on recent progress in research on tau and our understanding of the pathomechanisms of tau mediated neurodegeneration.