- Email: [email protected]
T52. Mismatch negativity in the diagnosis of Alzheimer disease
Abstracts / Clinical Neurophysiology 129 (2018) e1–e65
both types of movement are differently affected in PD patients with FOG. A recent study from our group demonstrated that the oscillatory activity within the subthalamic nucleus (STN) differs between patients with and without FOG (Storzer L et al., Bicycling suppresses abnormal beta synchrony in the Parkinsonian basal ganglia, Ann Neurol 2017). In particular, it was shown that patients with FOG present a characteristic increase of oscillatory activity at 18 Hz. The aim of the study was to examine movement-associated cortical oscillatory activity in PD patients with and without FOG. Methods: We analyzed EEG data of 19 PD patients with FOG (65.5 ± 7.2 years), 13 PD patients without FOG (61.6 ± 8.1 years), and 16 healthy controls (63.3 ± 7.3 years). Patients were recorded OFF dopaminergic medication using a portable EEG system (Porti, TMSi, Enschede, The Netherlands). Data were recorded during unconstrained walking and bicycling on a stationary bicycle. Measurements consisted of a baseline rest period, continuous movement, and an alternating sequence of rest and movement, i.e. bicycling or walking, for 10 s each. Furthermore, measurements included 180° turns around the body axis during walking condition. Turns were rated for the occurrence of FOG episodes by two different raters. Analyses were focused on oscillatory activity in the beta band and the Cz electrode overlying the leg area of both motor cortices. Statistical testing was performed by fitting linear mixed models using package lme 1.1–13 for R. Results: Bicycling and walking were associated with beta power suppression (13–35 Hz). This suppression was stronger for bicycling than for walking (b = 0.37, p < 0.001). Even though there were differences in behavioral data, such as cadence and pace between patients with FOG and patients without FOG, no difference in cortical power between patients with FOG and patients without FOG could be observed (b = 0.11, p = 0.72). Furthermore, within the group of Freezers we did not find cortical differences between turns with FOG and turns without FOG either(b = 0.66, p = 0.4). Conclusion: We did not observe cortical beta power changes specifically related to freezing. This finding does not support the notion that the primary motor cortex is crucially involved in generating freezing. doi:10.1016/j.clinph.2018.04.051
T51. TMS evaluation in cognitive impaired patients according to new criteria for AD—Francesco Di Lorenzo *, Caterina Motta, Viviana Ponzo, Alessandro Martorana, Giacomo Koch (Italy) ⇑
Presenting author.
Introduction: Alzheimer‘s disease (AD) is characterized by loss of synaptic connections, cell death and disruption of structural and functional networks. One of the most consistent findings is the impairment of cortical plasticity, especially Long Term Potentiation (LTP) mechanisms. Recently, the use of a new lexicon and new diagnostic criteria allowed to considered AD as a clinico-biological entity identifiable in vivo on the presence of biomarkers. In light of the new lexicon and the new diagnostic criteria, aim of the current work is to investigate cortical plasticity in cognitive impaired (CI) patients admitted for the first time in the memory clinic and stratified according to CSF biomarker profile; moreover we followed patients up to a period of three years to explore the relationship between neurophysiological, neuropsychological and CSF biomarker and clinical progression. Methods: Seventy-one consecutive patients recruited at the memory clinic admitted for their first visit for complaining memory symptoms and underwent CSF sampling. Then they undertake TMS examination, investigating mechanisms of long term potentiation
e21
(LTP) with intermittent Theta Busrt Stimluation (iTBS) and intracortical circuits. Patients were followed longitudinally with MMSE testing up to 36 months. According to the new criteria AD proposed we divided CI patients in basis of evidence ofin vivobiomarkers (as assessed by CSF analysis) and the presence of dementia. Resulting in three groups: (1) Mild Cognitive Impaired (MCI) patients (n = 22); Prodromal AD (PROAD) patients (n = 25); AD Dementia (ADD) patients (n = 25). Univariate regression analyses were performed to characterize the association between each clinical and neurophysiological variable with clinical progression (delta MMSE score at 36 months respect to baseline). A control group of 23 healthy subjects (HS) was recruited for control. Results: For neurophysiological evaluations only iTBS protocol was different among the different groups showing a paradoxical reversal of LTP for ADD and PROAD and a poor response for MCI patients. ProAD worsened faster than MCI. Regression analyses showed that LTP impairment was related to clinical progression. Kaplan-Meyer analyses showed that CI patients expressing the worst LTP values were the ones to progress faster in a 3 year time. Conclusion: the new criteria based on the presence of biomarkers and dementia allow us to identify CI patients at a prodromal stage that will develop dementia due to AD. LTP impairment drives the clinical progression in CI patients at prodromal stages even without evidence of biomarker positivity, confirming its pivotal role in determining cognitive decline. doi:10.1016/j.clinph.2018.04.052
T52. Mismatch negativity in the diagnosis of Alzheimer disease— Jui-Cheng Chen 1,*, Antonella Macerollo 2, Mark Edwards 2 (1 Taiwan, 2 United Kingdom) ⇑
Presenting author.
Introduction: Dementia is the major health issue in aging society. Among which, Alzheimer disease is the leading cause of dementia. The accumulation of amyloid plague causes the possible neurotoxicity of the brain particularly in hippocampus area, which results in the short-term memory loss as the early clinical symptom of the Alzheimer disease. The abnormal plasticity related to the NMDA receptor lies in the underlying mechanism of functional abnormality. Mismatch negativity (MMN) is an event related potential reflecting the automatic novel detection in our brain which related to frontotemporal circuits. It could be meliorated by the NMDA blockade. Here, we tried to use MMN as a biomarker for the detection of functional abnormality in Alzheimer disease. Methods: Total 25 healthy normal controls (6 Males and 19 Females) and 25 AD patients (10 Males and 15 Females) were completely collected. We recorded auditory MMN with four-deviant protocol with 32-channel EEG. Table 1 showed the individual MMSE score and profile of the patients. Results: In Fig. 1, the MMN component was identified as the peak negative wave within the 150–250 ms latency range. We evaluated the peak amplitude and peak latency of MMN at the Fz electrode. Table 2 showed the average latency and amplitude of MMN in controls and dementia patients. A significant difference was noted in protocol 3 (p = 0.03, independent t-test) and a trend of significance in protocol 2 and 4 (p = 0.06, p = 0.07). Fig. 2 showed the relative change of normalized Mismatch Negativity amplitude in responsive to the protocol change. There was a trend of increasing ratio in normal subjects but not in dementia patients. Conclusion: In consistence with other papers, we found reduced MMN in dementia patients, which may related to abnormal NMDA related plasticity change due to short-term memory impairment.
e22
Abstracts / Clinical Neurophysiology 129 (2018) e1–e65
Of interest, we also found the increasing trend of normalized Mismatch Negativity amplitude in responsive to the protocol change in normal subjects but not in dementia patients. This novel results serve a possible biomarker in the detection of functional abnormality in dementia patients.
T54. The difference of contralateral motor overflow according to spasticity among people with stroke—Joon-Ho Shin 1,*, Ji-Yeong Lee 1, Won-Kyung Song 1, Kyung Koh 2, Jae Kun Shim 2 (1 Republic of Korea, 2 USA)
doi:10.1016/j.clinph.2018.04.053
Introduction: Contralateral motor overflow is known as overt involuntary movement from accompanied contralateral production of voluntary movement. The prevalence of motor overflow is high in patients with stroke. Many previous studies were reported, however there is lack of studies about the relationship between motor overflow and spasticity or musculoskeletal factor. The objective of the present study was to investigate the contralateral motor overflow in patients with stroke during finger force production tasks in terms of spasticity and musculoskeletal factor. Methods: Forty-four patients with stroke, and 20 healthy control were participated in this study. Participants were seated and requested to put all fingers of both hands on force sensors (FUTEK) with various musculoskeletal factors (wrist posture: flexed, neutral, and extended posture) and speed (fast, slow). They produced maximum isometric pressing force with all fingers of right or left hand and the forces were recorded. We analyzed motor overflow magnitude, which is defined as the ratio of the non-task hand force to the corresponding task hand finger force. The spasticity was graded as modified Ashworth scale and we define that of healthy control as 0. Results: Motor overflow was different according to spasticity and the difference was consistent regardless of wrist posture and speed (all, p < 0.05). In addition, motor overflow was different depending on the finger flexion speed regardless of wrist posture (all, p < 0.05). Conclusion: We conclude that contralateral motor overflow during maximum force production tasks is dependent on the spasticity and speed of finger flexion regardless of physical wrist posture. Therefore, contralateral motor overflow could result from upper motor neuron lesion other than musculoskeletal facots.
T53. LTP-like cortical plasticity is associated with memory and predicts cognitive decline in Alzheimer’s disease patients— Francesco Di Lorenzo *, Caterina Motta, Viviana Ponzo, Giacomo Koch (Italy) ⇑
Presenting author.
Introduction: To determine the ability of transcranial magnetic stimulation (TMS) in detecting synaptic impairment in Alzheimer’s disease (AD) patients and predicting cognitive decline since the early phases of the disease. Methods: We evaluated long-term potentiation (LTP)-like cortical plasticity in 60 newly diagnosed AD patients. Pearson r correlation coefficient or Kruskal-Wallis runk sum test explored any relationship between LTP, demographics, cognition and AD-related biomarkers. Univariable analyses examined the association between LTP (respect to other AD-related biomarkers) and cognitive decline. Multivariable regression model revealed the best parameters able to predict disease progression. Results: LTP plasticity was not significantly associated with sex (z = 0.89, p = 0.37), age (r = 0.02, p = 0.75) or APOE genotype (z = 0.81, p = 0.41). We confirm a significant association between LTP and both CSF t-tau (r = 0.34, p < 0.01) and p-tau levels (r = 0.26, p = 0.04), while no significant association was find for Ab1–42 (r = 0.01, p = 0.89). Higher values of LTP were associated with higher long-term verbal memory performances (CVLT delayed: r = 0.45; p = 0.002), while neither visual-spatial long-term memory (RCF delayed: r = 0.08; p = 0.53), general intelligence (RPM test: r = 0.11; p = 0.45), executive functions (FVF: r = 0.13; p = 0.36) or visual-spatial abilities (RCF copy: r = 0.08; p = 0.54) showed any association. Among AD patients, higher values of LTP were associated with better long-term verbal memory performances (r = 0.45; p = 0.002). Notably, LTP was a significant predictor of disease progression (p = 0.02), while no other neurophysiological, neuropsychological and demographic parameters, was associated with cognitive decline, except for a trend regarding sex (p = 0.07), long-term verbal memory (p = 0.07), visuospatial abilities (p = 0.10) and CSF total-tau levels (p = 0.09). Multivariable analysis then promoted LTP as the best significant predictor of cognitive decline (p = 0.01). Conclusion: Synaptic dysfunction may be an early pathologic process in AD, and could be easily detected by means of TMS. Our data showed a significant correlation between episodic memory and LTPlike cortical plasticity, reinforcing the notion that this measure could be a neurophysiological surrogate of memory. Furthermore, our data show that LTP-like cortical plasticity is able alone to predict cognitive decline in AD patients. TMS could be a viable tool to assess synaptic impairment in AD patients, with LTP-like plasticity as the most sensitive marker of memory and predictor of cognitive decline progression.
doi:10.1016/j.clinph.2018.04.054
⇑
Presenting author.
doi:10.1016/j.clinph.2018.04.055
T55. Occipital seizures can cause focal neurological deficits and perceived delirium in the ICU patient—Jing Wang *, Subhashini Ramesh, Asma Zakaria (USA) ⇑
Presenting author.
Introduction: We discuss two cases of occipital seizures after neurological intervention presenting initially as complete or partial blindness and subsequently hallucinations. Methods: The patients underwent continuous EEG monitoring in the ICU as part of their workup. Results: Seizures arising from the occipital lobes were identified. Blindness resolved as seizure frequency decreased. The patients developed various forms of visual hallucinations with associated ictal EEG patterns after resolution of blindness. Conclusion: Post ictal blindness is analogous to Todd’s paralysis after motor seizures and may represent ongoing ictal activity in the post neurosurgical patient. Reports of hallucinations as well as blindness may be attributed to delirium and patients may go untreated for prolonged periods of time if undiagnosed. A high index of suspicion is needed if these symptoms are present in conjunction, and CEEG should be employed early in the workup. Ongoing neurological injury, worsening morbidity, unnecessary testing and prolonged LOS can be avoided with timely diagnosis and treatment. doi:10.1016/j.clinph.2018.04.056
both types of movement are differently affected in PD patients with FOG. A recent study from our group demonstrated that the oscillatory activity within the subthalamic nucleus (STN) differs between patients with and without FOG (Storzer L et al., Bicycling suppresses abnormal beta synchrony in the Parkinsonian basal ganglia, Ann Neurol 2017). In particular, it was shown that patients with FOG present a characteristic increase of oscillatory activity at 18 Hz. The aim of the study was to examine movement-associated cortical oscillatory activity in PD patients with and without FOG. Methods: We analyzed EEG data of 19 PD patients with FOG (65.5 ± 7.2 years), 13 PD patients without FOG (61.6 ± 8.1 years), and 16 healthy controls (63.3 ± 7.3 years). Patients were recorded OFF dopaminergic medication using a portable EEG system (Porti, TMSi, Enschede, The Netherlands). Data were recorded during unconstrained walking and bicycling on a stationary bicycle. Measurements consisted of a baseline rest period, continuous movement, and an alternating sequence of rest and movement, i.e. bicycling or walking, for 10 s each. Furthermore, measurements included 180° turns around the body axis during walking condition. Turns were rated for the occurrence of FOG episodes by two different raters. Analyses were focused on oscillatory activity in the beta band and the Cz electrode overlying the leg area of both motor cortices. Statistical testing was performed by fitting linear mixed models using package lme 1.1–13 for R. Results: Bicycling and walking were associated with beta power suppression (13–35 Hz). This suppression was stronger for bicycling than for walking (b = 0.37, p < 0.001). Even though there were differences in behavioral data, such as cadence and pace between patients with FOG and patients without FOG, no difference in cortical power between patients with FOG and patients without FOG could be observed (b = 0.11, p = 0.72). Furthermore, within the group of Freezers we did not find cortical differences between turns with FOG and turns without FOG either(b = 0.66, p = 0.4). Conclusion: We did not observe cortical beta power changes specifically related to freezing. This finding does not support the notion that the primary motor cortex is crucially involved in generating freezing. doi:10.1016/j.clinph.2018.04.051
T51. TMS evaluation in cognitive impaired patients according to new criteria for AD—Francesco Di Lorenzo *, Caterina Motta, Viviana Ponzo, Alessandro Martorana, Giacomo Koch (Italy) ⇑
Presenting author.
Introduction: Alzheimer‘s disease (AD) is characterized by loss of synaptic connections, cell death and disruption of structural and functional networks. One of the most consistent findings is the impairment of cortical plasticity, especially Long Term Potentiation (LTP) mechanisms. Recently, the use of a new lexicon and new diagnostic criteria allowed to considered AD as a clinico-biological entity identifiable in vivo on the presence of biomarkers. In light of the new lexicon and the new diagnostic criteria, aim of the current work is to investigate cortical plasticity in cognitive impaired (CI) patients admitted for the first time in the memory clinic and stratified according to CSF biomarker profile; moreover we followed patients up to a period of three years to explore the relationship between neurophysiological, neuropsychological and CSF biomarker and clinical progression. Methods: Seventy-one consecutive patients recruited at the memory clinic admitted for their first visit for complaining memory symptoms and underwent CSF sampling. Then they undertake TMS examination, investigating mechanisms of long term potentiation
e21
(LTP) with intermittent Theta Busrt Stimluation (iTBS) and intracortical circuits. Patients were followed longitudinally with MMSE testing up to 36 months. According to the new criteria AD proposed we divided CI patients in basis of evidence ofin vivobiomarkers (as assessed by CSF analysis) and the presence of dementia. Resulting in three groups: (1) Mild Cognitive Impaired (MCI) patients (n = 22); Prodromal AD (PROAD) patients (n = 25); AD Dementia (ADD) patients (n = 25). Univariate regression analyses were performed to characterize the association between each clinical and neurophysiological variable with clinical progression (delta MMSE score at 36 months respect to baseline). A control group of 23 healthy subjects (HS) was recruited for control. Results: For neurophysiological evaluations only iTBS protocol was different among the different groups showing a paradoxical reversal of LTP for ADD and PROAD and a poor response for MCI patients. ProAD worsened faster than MCI. Regression analyses showed that LTP impairment was related to clinical progression. Kaplan-Meyer analyses showed that CI patients expressing the worst LTP values were the ones to progress faster in a 3 year time. Conclusion: the new criteria based on the presence of biomarkers and dementia allow us to identify CI patients at a prodromal stage that will develop dementia due to AD. LTP impairment drives the clinical progression in CI patients at prodromal stages even without evidence of biomarker positivity, confirming its pivotal role in determining cognitive decline. doi:10.1016/j.clinph.2018.04.052
T52. Mismatch negativity in the diagnosis of Alzheimer disease— Jui-Cheng Chen 1,*, Antonella Macerollo 2, Mark Edwards 2 (1 Taiwan, 2 United Kingdom) ⇑
Presenting author.
Introduction: Dementia is the major health issue in aging society. Among which, Alzheimer disease is the leading cause of dementia. The accumulation of amyloid plague causes the possible neurotoxicity of the brain particularly in hippocampus area, which results in the short-term memory loss as the early clinical symptom of the Alzheimer disease. The abnormal plasticity related to the NMDA receptor lies in the underlying mechanism of functional abnormality. Mismatch negativity (MMN) is an event related potential reflecting the automatic novel detection in our brain which related to frontotemporal circuits. It could be meliorated by the NMDA blockade. Here, we tried to use MMN as a biomarker for the detection of functional abnormality in Alzheimer disease. Methods: Total 25 healthy normal controls (6 Males and 19 Females) and 25 AD patients (10 Males and 15 Females) were completely collected. We recorded auditory MMN with four-deviant protocol with 32-channel EEG. Table 1 showed the individual MMSE score and profile of the patients. Results: In Fig. 1, the MMN component was identified as the peak negative wave within the 150–250 ms latency range. We evaluated the peak amplitude and peak latency of MMN at the Fz electrode. Table 2 showed the average latency and amplitude of MMN in controls and dementia patients. A significant difference was noted in protocol 3 (p = 0.03, independent t-test) and a trend of significance in protocol 2 and 4 (p = 0.06, p = 0.07). Fig. 2 showed the relative change of normalized Mismatch Negativity amplitude in responsive to the protocol change. There was a trend of increasing ratio in normal subjects but not in dementia patients. Conclusion: In consistence with other papers, we found reduced MMN in dementia patients, which may related to abnormal NMDA related plasticity change due to short-term memory impairment.
e22
Abstracts / Clinical Neurophysiology 129 (2018) e1–e65
Of interest, we also found the increasing trend of normalized Mismatch Negativity amplitude in responsive to the protocol change in normal subjects but not in dementia patients. This novel results serve a possible biomarker in the detection of functional abnormality in dementia patients.
T54. The difference of contralateral motor overflow according to spasticity among people with stroke—Joon-Ho Shin 1,*, Ji-Yeong Lee 1, Won-Kyung Song 1, Kyung Koh 2, Jae Kun Shim 2 (1 Republic of Korea, 2 USA)
doi:10.1016/j.clinph.2018.04.053
Introduction: Contralateral motor overflow is known as overt involuntary movement from accompanied contralateral production of voluntary movement. The prevalence of motor overflow is high in patients with stroke. Many previous studies were reported, however there is lack of studies about the relationship between motor overflow and spasticity or musculoskeletal factor. The objective of the present study was to investigate the contralateral motor overflow in patients with stroke during finger force production tasks in terms of spasticity and musculoskeletal factor. Methods: Forty-four patients with stroke, and 20 healthy control were participated in this study. Participants were seated and requested to put all fingers of both hands on force sensors (FUTEK) with various musculoskeletal factors (wrist posture: flexed, neutral, and extended posture) and speed (fast, slow). They produced maximum isometric pressing force with all fingers of right or left hand and the forces were recorded. We analyzed motor overflow magnitude, which is defined as the ratio of the non-task hand force to the corresponding task hand finger force. The spasticity was graded as modified Ashworth scale and we define that of healthy control as 0. Results: Motor overflow was different according to spasticity and the difference was consistent regardless of wrist posture and speed (all, p < 0.05). In addition, motor overflow was different depending on the finger flexion speed regardless of wrist posture (all, p < 0.05). Conclusion: We conclude that contralateral motor overflow during maximum force production tasks is dependent on the spasticity and speed of finger flexion regardless of physical wrist posture. Therefore, contralateral motor overflow could result from upper motor neuron lesion other than musculoskeletal facots.
T53. LTP-like cortical plasticity is associated with memory and predicts cognitive decline in Alzheimer’s disease patients— Francesco Di Lorenzo *, Caterina Motta, Viviana Ponzo, Giacomo Koch (Italy) ⇑
Presenting author.
Introduction: To determine the ability of transcranial magnetic stimulation (TMS) in detecting synaptic impairment in Alzheimer’s disease (AD) patients and predicting cognitive decline since the early phases of the disease. Methods: We evaluated long-term potentiation (LTP)-like cortical plasticity in 60 newly diagnosed AD patients. Pearson r correlation coefficient or Kruskal-Wallis runk sum test explored any relationship between LTP, demographics, cognition and AD-related biomarkers. Univariable analyses examined the association between LTP (respect to other AD-related biomarkers) and cognitive decline. Multivariable regression model revealed the best parameters able to predict disease progression. Results: LTP plasticity was not significantly associated with sex (z = 0.89, p = 0.37), age (r = 0.02, p = 0.75) or APOE genotype (z = 0.81, p = 0.41). We confirm a significant association between LTP and both CSF t-tau (r = 0.34, p < 0.01) and p-tau levels (r = 0.26, p = 0.04), while no significant association was find for Ab1–42 (r = 0.01, p = 0.89). Higher values of LTP were associated with higher long-term verbal memory performances (CVLT delayed: r = 0.45; p = 0.002), while neither visual-spatial long-term memory (RCF delayed: r = 0.08; p = 0.53), general intelligence (RPM test: r = 0.11; p = 0.45), executive functions (FVF: r = 0.13; p = 0.36) or visual-spatial abilities (RCF copy: r = 0.08; p = 0.54) showed any association. Among AD patients, higher values of LTP were associated with better long-term verbal memory performances (r = 0.45; p = 0.002). Notably, LTP was a significant predictor of disease progression (p = 0.02), while no other neurophysiological, neuropsychological and demographic parameters, was associated with cognitive decline, except for a trend regarding sex (p = 0.07), long-term verbal memory (p = 0.07), visuospatial abilities (p = 0.10) and CSF total-tau levels (p = 0.09). Multivariable analysis then promoted LTP as the best significant predictor of cognitive decline (p = 0.01). Conclusion: Synaptic dysfunction may be an early pathologic process in AD, and could be easily detected by means of TMS. Our data showed a significant correlation between episodic memory and LTPlike cortical plasticity, reinforcing the notion that this measure could be a neurophysiological surrogate of memory. Furthermore, our data show that LTP-like cortical plasticity is able alone to predict cognitive decline in AD patients. TMS could be a viable tool to assess synaptic impairment in AD patients, with LTP-like plasticity as the most sensitive marker of memory and predictor of cognitive decline progression.
doi:10.1016/j.clinph.2018.04.054
⇑
Presenting author.
doi:10.1016/j.clinph.2018.04.055
T55. Occipital seizures can cause focal neurological deficits and perceived delirium in the ICU patient—Jing Wang *, Subhashini Ramesh, Asma Zakaria (USA) ⇑
Presenting author.
Introduction: We discuss two cases of occipital seizures after neurological intervention presenting initially as complete or partial blindness and subsequently hallucinations. Methods: The patients underwent continuous EEG monitoring in the ICU as part of their workup. Results: Seizures arising from the occipital lobes were identified. Blindness resolved as seizure frequency decreased. The patients developed various forms of visual hallucinations with associated ictal EEG patterns after resolution of blindness. Conclusion: Post ictal blindness is analogous to Todd’s paralysis after motor seizures and may represent ongoing ictal activity in the post neurosurgical patient. Reports of hallucinations as well as blindness may be attributed to delirium and patients may go untreated for prolonged periods of time if undiagnosed. A high index of suspicion is needed if these symptoms are present in conjunction, and CEEG should be employed early in the workup. Ongoing neurological injury, worsening morbidity, unnecessary testing and prolonged LOS can be avoided with timely diagnosis and treatment. doi:10.1016/j.clinph.2018.04.056