Background: Growing evidence suggests that pathological processes leading to Alzheimer's disease occurs gradually and begins to develop decades before the earliest clinical symptoms occur. The use of biomarkers has been proposed to detect evidence of preclinical Alzheimer's pathologic change in asymptomatic subjects. Subjective cognitive complaints (SCC) i.e. self-reported cognitive decline with normal cognition have been reported as an indicator of future cognitive decline, however, this condition is unspecific. Objective: In the present study we used the regional brain perfusion measured by HMPAO-SPECT as Biomarker of neurodegeneration to compare the regional brain perfusion of patient with subjective cognitive complaints with and without minimal cognitive dysfunction (SCC+ and SCC-respectively) in respect to patients with mild cognitive impairment (MCI). Methods: We retrospectively examined 736 Patients who referred to our Memory Clinic because of suspected cognitive dysfunction. After exclusion of patients with overt dementia, automated, quantitatively assessed relative cerebral blood flow of 10 forebrain regions (thalamus, parietotemporal, medial temporal, posterior temporal, posterior cingulate gyrus, each region left hemispheric and right hemispheric) and neuropsychological assessment of 64 SCC (32 SCC+; 32 SCC-) and 28 MCI subjects were analysed. Results:. The most relevant differences between groups in cognitive performance concerned verbal memory. Left hemispheric medial temporal region could significantly discriminate between all three groups, with a progressive decrease n perfusion from SCC towards MCI. Area under the curve of left medial temporal region showed a sensitivity of 0,61 and a specificity of 0,78 for discriminating MCI from SCC. Conclusion: Automated analysis of HMPAO-SPECT data of MCI and SCC+ patients showed significant perfusion differences in medial temporal region and impaired verbal memory, both of which are known features of Alzheimer's disease. Perfusion patterns and verbal memory performance in SCC+ are more similar to MCI than SCC-. Thus, SPECT analysis could distinguish those subjects whose perfusion pattern resembles that of an MCI from those who do not. In our opinion, this could identify two populations with a different risk of progression to AD, with SCC+ subjects needing further diagnostic examination and repeated follow-up.

STUDY DESIGN:Topical review of the literature.OBJECTIVE:The objective of this review article was to assess indications and usefulness of various neurophysiological techniques in diagnosis and management of cervical spondylogenic myelopathy (CSM).METHODS:The MEDLINE, accessed by Pubmed and EMBASE electronic databases, was searched using the medical subject headings: 'compressive myelopathy', 'cervical spondylotic myelopathy (CSM)', 'cervical spondylogenic myelopathy', 'motor evoked potentials (MEPs)', 'transcranial magnetic stimulation', 'somatosensory evoked potentials (SEPs)', 'electromyography (EMG)', 'nerve conduction studies (NCS)' and 'cutaneous silent period (CSP)'.RESULTS:SEPs and MEPs recording can usefully supplement clinical examination and neuroimaging findings in assessing the spinal cord injury level and severity. Segmental cervical cord dysfunction can be revealed by an abnormal spinal N13 response, whereas the P14 potential is a reliable marker of dorsal column impairment. MEPs may also help in the differential diagnosis between spinal cord compression and neurodegenerative disorders. SEPs and MEPs are also useful in follow-up evaluation of sensory and motor function during surgical treatment and rehabilitation. EMG and NCS improve the sensitivity of cervical radiculopathy detection and may help rule out peripheral nerve problems that can cause symptoms that are similar to those of CSM. CSP also shows a high sensitivity for detecting CSM.CONCLUSION:Neuroimaging, especially magnetic resonance imaging, represents the procedure of choice for the diagnosis of CSM, but a correct interpretation of morphological findings can be achieved only if they are correlated with functional data. The studies reported in this review highlight the crucial role of the electrophysiological studies in diagnosis and management of CSM.

Arousal, or wakefulness, is an integral component of consciousness and prerequisite for other brain functions, yet its neuroanatomy in humans is poorly understood. Classically, the brainstem "reticular formation" has been considered important for wakefulness.1 Experiments in rodents suggest this brainstem area can be subdivided into functionally discrete regions, and that injury to one region in the pontine tegmentum reliably disrupts arousal and produces coma.2 A homologous brainstem region is likely present in humans, based on analysis of coma-causing lesions.3 However, it remains unclear whether there is a human brainstem site significantly more associated with coma-causing lesions than with non–coma-causing lesions, and exactly where this site is located. Such a brainstem site would likely maintain arousal through ascending projections to other brain regions (originally termed the ascending reticular activating system, or ARAS),1,4 but this network of brain regions in humans is also unclear.

Study design: Repetitive transcranial magnetic stimulation study. Objectives: The analgesic effects of repetitive transcranial magnetic stimulation (rTMS) in chronic pain have been the focus of several studies. In particular, rTMS of the premotor cortex/dorsolateral prefrontal cortex (PMC/DLPFC) changes pain perception in healthy subjects and has analgesic effects in acute postoperative pain, as well as in fibromyalgia patients. However, its effect on neuropathic pain in patients with traumatic spinal cord injury (SCI) has not been assessed. Setting: Merano (Italy) and Salzburg (Austria). Methods: In this study, we performed PMC/DLPFC rTMS in subjects with SCI and neuropathic pain. Twelve subjects with chronic cervical or thoracic SCI were randomized to receive 1250 pulses at 10 Hz rTMS ( n =6) or sham rTMS ( n =6) treatment for 10 sessions over 2 weeks. The visual analog scale, the sensory and affective pain rating indices of the McGill Pain Questionnaire (MPQ), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale were used to assed pain and mood at baseline (T0), 1 day after the first week of treatment (T1), 1 day (T2), 1 week (T3) and 1 month (T4) after the last intervention. Results: Subjects who received active rTMS had a statistically significant reduction in pain symptoms in comparison with their baseline pain, whereas sham rTMS participants had a non-significant change in daily pain from their baseline pain. Conclusion: The findings of this preliminary study in a small patient sample suggest that rTMS of the PMC/DLPFC may be effective in relieving neuropathic pain in SCI patients.

STUDY DESIGN:Transcranial magnetic stimulation study.OBJECTIVES:To further investigate the corticospinal excitability changes after spinal cord injury (SCI), as assessed by means of transcranial magnetic stimulation (TMS).SETTING:Merano (Italy) and Salzburg (Austria).METHODS:We studied resting motor threshold (RMT), motor evoked potential (MEP) amplitude and recruitment curve in five subjects with good recovery after traumatic incomplete cervical SCI.RESULTS:RMT did not differ significantly between patients and controls, whereas the slope of MEP recruitment curve was significantly increased in the patients.CONCLUSION:This abnormal finding may represent an adaptive response after SCI. The impaired ability of the motor cortex to generate proper voluntary movement may be compensated by increasing spinal excitability. The easily performed measurement of MEP recruitment curve may provide a useful additional tool to improve the assessment and monitoring of motor cortical function in subjects with SCI. Increasing our knowledge of the corticospinal excitability changes in the functional recovery after SCI may also support the development of effective therapeutic strategies.

STUDY DESIGN:Experimental neurophysiological study.OBJECTIVES:The hepatic myelopathy (HM) is characterized by progressive weakness and spasticity of the lower extremities, while there are only a few reports of sensory impairment. However, sensory function has been poorly explored in HM. We believe that an electrophysiological assessment of dorsal columns by somatosensory evoked potentials (SEPs) and of cortico-spinal lateral tracts by motor evoked potentials (MEPs) should be of considerable value in the functional evaluation of the spinal cord involvement in patients with HM.SETTING:Salzburg (Austria) and Merano (Italy).METHODS:Eight patients diagnosed with HM were studied with MEPs and SEPs. Neurological examination revealed different degrees of cortico-spinal tract involvement in all patients and sensory abnormalities in three patients.RESULTS:Central motor conduction to lower limb muscles was abnormal in all patients, while central sensory conduction was abnormal in seven out of the eight patients. Both central motor and sensory conduction to upper limbs are normal in all patients.CONCLUSION:The main finding is that electrophysiological evidence of central sensory involvement is present in a very high percentage of patients with HM, and that the threshold for electrophysiological abnormalities is below that for clinical manifestations. Therefore, central sensory and motor conduction studies are sensitive methods for detecting, localizing and monitoring spinal cord damage in HM.

Several Transcranial Magnetic Stimulation (TMS) techniques can be applied to noninvasively measure cortical excitability and brain plasticity in humans. TMS has been used to assess neuroplastic changes in Alzheimer's disease (AD), corroborating findings that cortical physiology is altered in AD due to the underlying neurodegenerative process. In fact, many TMS studies have provided physiological evidence of abnormalities in cortical excitability, connectivity, and plasticity in patients with AD. Moreover, the combination of TMS with other neurophysiological techniques, such as high-density electroencephalography (EEG), makes it possible to study local and network cortical plasticity directly. Interestingly, several TMS studies revealed abnormalities in patients with early AD and even with mild cognitive impairment (MCI), thus enabling early identification of subjects in whom the cholinergic degeneration has occurred. Furthermore, TMS can influence brain function if delivered repetitively; repetitive TMS (rTMS) is capable of modulating cortical excitability and inducing long-lasting neuroplastic changes. Preliminary findings have suggested that rTMS can enhance performances on several cognitive functions impaired in AD and MCI. However, further well-controlled studies with appropriate methodology in larger patient cohorts are needed to replicate and extend the initial findings. The purpose of this paper was to provide an updated and comprehensive systematic review of the studies that have employed TMS/rTMS in patients with MCI and AD.

Correction to: Spinal Cord (2014) 52, S23–S24; doi:10.1038/sc.2013.165; published online 14 January 2014 Since the publication of this paper, the authors have realized that one of the author names was misspelled. S Golaszweski should have appeared as S Golaszewski. The corrected author list is shownhere.

STUDY DESIGN:Randomized, double-blind, crossover, sham-controlled trial.OBJECTIVES:Repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) leads to a significant reduction of spasticity in subjects with spinal cord injury (SCI), but the physiological basis of this effect is still not well understood. The purpose of this study was to evaluate the disynaptic reciprocal Ia inhibition of soleus motoneurons in SCI patients.SETTING:Department of Neurology, Merano, Italy and TMS Laboratory, Paracelsus Medical University, Salzburg, Austria.METHODS:Nine subjects with incomplete cervical or thoracic SCI received 5 days of daily sessions of real or sham rTMS applied over the contralateral M1. We compared the reciprocal inhibition, the Modified Ashworth Scale and the Spinal Cord Injury Assessment Tool for Spasticity at baseline, after the last session and 1 week later in the real rTMS and sham stimulation groups.RESULTS:We found that real rTMS significantly reduced lower limb spasticity and restored the impaired excitability in the disynaptic reciprocal inhibitory pathway.CONCLUSIONS:In a small proof-of-concept study, rTMS strengthened descending projections between the motor cortex and inhibitory spinal interneuronal circuits. This reversed a defect in reciprocal inhibition after SCI, and reduced leg spasticity.