We thank dr. Coebergh and colleagues for their interest in our study. We agree that(a) there are many differences between the health care systems of the UK and the Netherlands, (b) the results of our study do not apply to excluded patients, and (c) the management of new neurological symptoms, relapses of previous FNS and relevant neurological and other co-morbidities remain very important in order to prevent inappropriate re-referrals and investigations of patients. However, in the absence of sound evidence from appropriate clinical studies,we disagree with the authors’ conclusion that neurological follow-up of these patients is often beneficial.
We wish to emphasize that in our study, firstly a neurologist established the diagnosis and briefly explained the diagnosis to the patient. Secondly, the first neurologist referred the patient to a specially trained second neurologist, who scheduled half an hour to discuss the diagnosis with the patient. This approach is clearly different from immediate referral to a GP after the diagnosis.
Li-Qin Sheng1, Ping-Lei Pan2
1 Department of Neurology, Traditional Chinese Medicine Hospital of Kunshan, Kunshan, PR China
2 Department of Neurology, Affiliated Yancheng Hospital, School of Medicine, Southeast University, Yancheng, PR China
Correspondence:
PingLei Pan, Department of Neurology, Affiliated Yancheng Hospital, School of Medicine, Southeast University, West Xindu Road 2#, Yancheng, Jiangsu Province, 224001, PR China. E-mail: panpinglei@163.com, Telephone: +8618361146977
Coordinate-based meta-analysis is a powerful way for neuroimaging studies to identify the most consistent and replicable differences in brain activity or structure in neurodegenerative disorders. In their JNNP publication, Gellersen et al 1 conducted coordinate-based meta-analyses of 54 voxel-based morphometry (VBM) studies in Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), behavioral variant frontotemporal dementia (bvFTD), amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). In this study, they solely focused on cerebellar grey matter (GM) atrophy.1 Marked cerebellar atrophy in AD, ALS, bvFTD, PSP and MSA, but not in PD or HD, was identified in the meta-analyses.1
These findings are of interest.1 However, the procedure of the meta-analyses had a major limitation. Coordin...
Li-Qin Sheng1, Ping-Lei Pan2
1 Department of Neurology, Traditional Chinese Medicine Hospital of Kunshan, Kunshan, PR China
2 Department of Neurology, Affiliated Yancheng Hospital, School of Medicine, Southeast University, Yancheng, PR China
Correspondence:
PingLei Pan, Department of Neurology, Affiliated Yancheng Hospital, School of Medicine, Southeast University, West Xindu Road 2#, Yancheng, Jiangsu Province, 224001, PR China. E-mail: panpinglei@163.com, Telephone: +8618361146977
Coordinate-based meta-analysis is a powerful way for neuroimaging studies to identify the most consistent and replicable differences in brain activity or structure in neurodegenerative disorders. In their JNNP publication, Gellersen et al 1 conducted coordinate-based meta-analyses of 54 voxel-based morphometry (VBM) studies in Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), behavioral variant frontotemporal dementia (bvFTD), amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). In this study, they solely focused on cerebellar grey matter (GM) atrophy.1 Marked cerebellar atrophy in AD, ALS, bvFTD, PSP and MSA, but not in PD or HD, was identified in the meta-analyses.1
These findings are of interest.1 However, the procedure of the meta-analyses had a major limitation. Coordinate-based meta-analysis is usually used for whole-brain imaging findings. Gellersen et al1 only included the studies that reported coordinates of the cerebellar regions, which resulted in study selection bias in the analyses. This bias may increase the statistical power and the risk of false positive findings in their study. The view is supported by previous meta-analyses in these disorders. Robust cerebellar atrophy was not detected in AD 2, ALS 3, bvFTD 4, PSP 5, PD 6, or HD 7 by previous meta-analyses that included many more whole-brain VBM studies. In contrast, cerebellar atrophy was consistently identified in MSA 5, which was accordant with the meta-analysis by Gellersen et al.1 Thus, selective use of a paticular brain region is not optimal in a coordinate-based meta-analysis.
Based on the current conflicting imaging evidence, it is debatable to consider the existence of cerebellar atrophy in AD, ALS, bvFTD and PSP in VBM studies. As clinical heterogeneity in these disorders and limited by the imaging techniques, further research is warranted to validate cerebellar atrophy in neurodegeneration.
Funding: This work was supported in part by the National Natural Science Foundation of China (Grant No. 81601161).
Competing interests: None.
Contributors: LQS wrote the draft. PLP revised the manuscript.
References:
1. Gellersen HM, Guo CC, O'Callaghan C, et al. Cerebellar atrophy in neurodegeneration-a meta-analysis. J Neurol Neurosurg Psychiatry 2017, in press.
2. Chapleau M, Aldebert J, Montembeault M, et al. Atrophy in Alzheimer's Disease and Semantic Dementia: An ALE Meta-Analysis of Voxel-Based Morphometry Studies. J Alzheimers Dis 2016;54(3):941-55.
3. Sheng L, Ma H, Zhong J, et al. Motor and extra-motor gray matter atrophy in amyotrophic lateral sclerosis: quantitative meta-analyses of voxel-based morphometry studies. Neurobiol Aging 2015;36(12):3288-99.
4. Schroeter ML, Laird AR, Chwiesko C, et al. Conceptualizing neuropsychiatric diseases with multimodal data-driven meta-analyses - the case of behavioral variant frontotemporal dementia. Cortex 2014;57:22-37.
5. Yu F, Barron DS, Tantiwongkosi B, et al. Patterns of gray matter atrophy in atypical parkinsonism syndromes: a VBM meta-analysis. Brain Behav 2015;5(6):e00329.
6. Shao N, Yang J, Shang H. Voxelwise meta-analysis of gray matter anomalies in Parkinson variant of multiple system atrophy and Parkinson's disease using anatomic likelihood estimation. Neurosci Lett 2015;587:79-86.
7. Dogan I, Eickhoff SB, Schulz JB, et al. Consistent neurodegeneration and its association with clinical progression in Huntington's disease: a coordinate-based meta-analysis. Neurodegener Dis 2013;12(1):23-35.
In our previous meta-analysis of cerebellar atrophy in seven major neurodegenerative conditions (Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Huntington’s disease (HD), Parkinson’s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP)) we investigated studies that reported grey matter (GM) loss in the cerebellum [1]. Consistent regions of atrophy were found in AD, ALS, FTD, MSA, and PSP but not HD or PD. In their comment on our meta-analysis, Sheng and Pan have argued that our method of selectively investigating studies that found cerebellar atrophy, rather than adopting a whole-brain approach, is “not optimal in a coordinate-based meta-analysis” [2]. They further cite previous whole-brain meta-analyses that did not identify clusters of cerebellar grey matter loss in patients [3-6].
Here, we argue that our approach was justified given our aim, which was to focus on cases where cerebellar atrophy was found in the respective disease groups in order to determine 1) if such atrophy followed a consistent, robust pattern, and 2) if atrophy patterns were disease-specific or generic, where possible relating them to symptomatology.
There are several reasons why we chose to focus on the cerebellum rather than adopting a whole-brain approach. First, the cerebellum is hardly a “region of interest” in the classical sense given its marked heterogeneity in terms of function and connectivity as we...
In our previous meta-analysis of cerebellar atrophy in seven major neurodegenerative conditions (Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Huntington’s disease (HD), Parkinson’s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP)) we investigated studies that reported grey matter (GM) loss in the cerebellum [1]. Consistent regions of atrophy were found in AD, ALS, FTD, MSA, and PSP but not HD or PD. In their comment on our meta-analysis, Sheng and Pan have argued that our method of selectively investigating studies that found cerebellar atrophy, rather than adopting a whole-brain approach, is “not optimal in a coordinate-based meta-analysis” [2]. They further cite previous whole-brain meta-analyses that did not identify clusters of cerebellar grey matter loss in patients [3-6].
Here, we argue that our approach was justified given our aim, which was to focus on cases where cerebellar atrophy was found in the respective disease groups in order to determine 1) if such atrophy followed a consistent, robust pattern, and 2) if atrophy patterns were disease-specific or generic, where possible relating them to symptomatology.
There are several reasons why we chose to focus on the cerebellum rather than adopting a whole-brain approach. First, the cerebellum is hardly a “region of interest” in the classical sense given its marked heterogeneity in terms of function and connectivity as well as its large cell count [7,8]. Using an ROI approach on the cerebellum is therefore not vastly different from conducting an analysis restricted to the neocortex, a practice that is abundant and well accepted. The vast majority of coordinates used in our analysis stemmed from whole-brain analyses and omitting the few studies with an ROI approach for the cerebellum is highly unlikely to affect the main clusters we identified.
Second, there is an abundance of coordinate-based meta-analyses using ROI approaches (see http://www.brainmap.org/pubs/), including one of the most influential papers into the functions of the cerebellum [8].
Third, the systematic literature search of papers investigating the diseases in question has revealed that many analyses were inherently biased against the cerebellum. As shown in our PRISMA flowchart, there was a tendency towards excluding the cerebellum (n=64) or not reporting or discussing cerebellar findings in text even when figures indicated the cerebellum was affected (n=13 for which we could not obtain data even after contacting authors). Twenty-seven studies further indicated potential cerebellar effects but did not report coordinates. These numbers made it clear that this bias in investigating the diseases of interest and in reporting results would inadvertently be translated into a bias in the meta-analytic results when choosing a whole-brain approach.
Given this abundance of studies excluding the cerebellum and underreporting cerebellar findings, it is not surprising that previous meta-analyses did not find robust clusters of cerebellar atrophy. Furthermore, there are additional factors that can explain the apparent lack of GM loss in the cerebellum in the AD, ALS, and FTD meta-analyses.
First, the majority of studies in AD and ALS investigated early stages, during which cerebellar atrophy may not yet be apparent. This tendency to investigate early structural changes may contribute to the belief that the cerebellum is typically spared. Given that clinical assessment using magnetic resonance imaging is carried out early in disease progression and that follow-up scans in clinical practice are rare, later GM loss often remains unexplored. However, neuropathological investigations have found the cerebellum to be affected in AD, ALS, and PSP [9-11]. Second, in our systematic literature search, we contacted authors to obtain additional coordinate data, which was not done in most of the other meta-analyses. The following should emphasize these arguments:
• AD meta-analysis [3]: did not include seven studies present in our analysis; of the 46 AD studies listed in Table 1, n=23 included exclusively early-stage/mild AD, and n=9 studies mild to moderate AD. One study with preclinical AD cases and another with a sample of MSA with dementia would not have met our inclusion criteria [12,13].
• FTD meta-analysis [4]: did not include nine studies from our analysis. 3/9 studies in the whole-brain analysis showed cerebellar atrophy; of the remaining six, n=3 included only patients with mild FTD severity, while n=1 included mild to moderate.
• ALS meta-analysis [5]: did not include two of the studies in our paper. 5/20 studies reported disease-related cerebellar grey matter (GM) or white matter integrity loss; of the other 15, n=10 focussed on patients with mild symptom severity. Interestingly, Minnerop et al. showed a correlation of cerebellar GM loss and disease duration, suggesting that the cerebellum is affected later in the course of ALS [14].
• We would like to point out that the PSP meta-analysis [6], which was cited by Sheng and Pan as not having detected cerebellar GM loss, did find a cluster of atrophy in right declive (see Table 2). This meta-analysis also did not include two of the studies incorporated in our investigation. Cerebellar GM loss was found in 5/12 studies in this meta-analysis, while n=4 of the remaining seven found white matter loss in cerebellar peduncles in the absence of GM differences. Of the three studies with no cerebellar findings, n=2 were in mild PSP.
Finally, we would like to emphasise that we are not claiming that cerebellar atrophy is necessarily present in the majority of patients in all of the investigated diseases. Given that we only selected studies with findings in the cerebellum, we did not seek to determine the likelihood of the cerebellum being affected in a given disease. For our purpose, a focus on studies with cerebellar findings is justified. We conclude that if cerebellar atrophy is present, it follows a disease-specific pattern that tends to correlate with symptomatology in many of the included studies. Our findings demonstrate the importance of future research into the role of the cerebellum in neurodegeneration given the two major issues in the literature which are the tendency to disregard the cerebellum and the vast heterogeneity of patient groups regarding disease stages and subtypes.
References
1. Gellersen HM, Guo CC, O’Callaghan C, et al. Cerebellar atrophy in neurodegeneration—a meta-analysis. J Neurol, Neurosurg Psychiatry 2017, in press.
2. Sheng L-Q, Pan P-L. Does Cerebellar Atrophy in Neurodegeneration? J Neurol, Neurosurg Psychiatry 2017. http://jnnp.bmj.com/content/early/2017/05/27/jnnp-2017-315607.responses
3. Chapleau M, Aldebert J, Montembeault M, Brambati SM. Atrophy in Alzheimer's Disease and Semantic Dementia: An ALE Meta-Analysis of Voxel-Based Morphometry Studies. J Alzheimers Dis 2016;54(3):941-55.
4. Schroeter ML, Laird AR, Chwiesko C, et al. Conceptualizing neuropsychiatric diseases with multimodal data-driven meta-analyses - the case of behavioral variant frontotemporal dementia. Cortex 2014;57:22-37.
5. Sheng L, Ma H, Zhong J, et al. Motor and extra-motor gray matter atrophy in amyotrophic lateral sclerosis: quantitative meta-analyses of voxel-based morphometry studies. Neurobiol Aging 2015;36(12):3288-99.
6. Yu F, Barron DS, Tantiwongkosi B, Fox P. Patterns of gray matter atrophy in atypical parkinsonism syndromes: a VBM meta-analysis. Brain Behav 2015;5(6):e00329.
7. Balsters JH, Laird AR, Fox PT, Eickhoff SB. Bridging the gap between functional and anatomical features of cortico-cerebellar circuits using meta-analytic connectivity modeling. Hum Brain Mapp 2014;35(7):3152-69.
8. Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: A meta-analysis of neuroimaging studies. NeuroImage 2009;44(2):489-501.
9. Kanazawa M, Shimohata T, Toyoshima Y, et al. Cerebellar involvement in progressive supranuclear palsy: A clinicopathological study. Mov Disord 2009;24(9):1312-8.
10. Larner AJ. The Cerebellum in Alzheimer's Disease. Dement Geriatr Cogn Disord 1997;8(4):203-9.
11. Prell T, Grosskreutz J. The involvement of the cerebellum in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degen 2013;14(7-8):507-15.
12. Hämäläinen A, Pihlajamäki M, Tanila H, et al. Increased fMRI responses during encoding in mild cognitive impairment. Neurobiol Aging 2007;28(12):1889-903.
13. Tondelli M, Wilcock GK, Nichelli P, et al. Structural MRI changes detectable up to ten years before clinical Alzheimer's disease. Neurobiol Aging 2012;33(4):825.e25-36.
14. Minnerop M, Specht K, Ruhlmann J, et al. In vivo voxel-based relaxometry in amyotrophic lateral sclerosis. J Neurol 2009;256(1):28-34.
It is good to see that trials are being done to answer the critical question of how best to provide care for those patients with functional neurological symptoms (FNS). The research paper, ‘Management of patients with functional neurological symptoms: a single-centre randomised controlled trial’, by Pleizier, de Haan and Vermeulen, randomizes outpatients with functional neurological symptoms after diagnosis, to either two outpatient appointments with a neurologist, or referral back to a GP. Intriguingly, it finds no difference in outcome, that is quality of life scores, between the two groups.[1] While this study attempts to address an important question, namely the role of the neurologist in the care of patients with functional neurological disorders, we feel it has a number of problems that limit its generalizability, particularly to UK neurology practice.
The Netherlands is a country that compared to the UK, has approximately four times as many neurologists per head of the population, and many more GPs with higher levels of job satisfaction,[2] and often have mental health nurse support in the practice itself. Neurology outpatient waiting times are shorter in the Netherlands, and in-patient neurology review happens routinely and is quicker, unlike in the UK where it may not occur at all.[3] Because of this lack of prompt neurological review in the UK, it is common for patients to receive erroneous diagnoses, often necessitating an “undiagnosis” at the eventual neu...
It is good to see that trials are being done to answer the critical question of how best to provide care for those patients with functional neurological symptoms (FNS). The research paper, ‘Management of patients with functional neurological symptoms: a single-centre randomised controlled trial’, by Pleizier, de Haan and Vermeulen, randomizes outpatients with functional neurological symptoms after diagnosis, to either two outpatient appointments with a neurologist, or referral back to a GP. Intriguingly, it finds no difference in outcome, that is quality of life scores, between the two groups.[1] While this study attempts to address an important question, namely the role of the neurologist in the care of patients with functional neurological disorders, we feel it has a number of problems that limit its generalizability, particularly to UK neurology practice.
The Netherlands is a country that compared to the UK, has approximately four times as many neurologists per head of the population, and many more GPs with higher levels of job satisfaction,[2] and often have mental health nurse support in the practice itself. Neurology outpatient waiting times are shorter in the Netherlands, and in-patient neurology review happens routinely and is quicker, unlike in the UK where it may not occur at all.[3] Because of this lack of prompt neurological review in the UK, it is common for patients to receive erroneous diagnoses, often necessitating an “undiagnosis” at the eventual neurology review.[4] Given these starkly different clinical contexts, we believe that a single neurology appointment in the UK, as compared to neurological follow-up for patients with FNS, would not lead to similar outcomes as published in this study.
Not withstanding these cultural differences, there is also significant, multi-faceted selection bias in this study, which limits the interpretation of the results. Firstly, the authors only include patients referred by GPs in this study. In our experience, patients that come via A&E or have been recently discharged from hospital are different to those referred by GPs, having had more investigations, and have more severe symptoms and a poorer prognosis if there is
no improvement in hospital.[5] The authors also exclude patients who have been symptomatic for over a year. In reality, this would mean the exclusion of large numbers of patients. Indeed in this study 923/1147 patients are excluded for this very reason,[1] and the proportion of patients is likely to be higher in the UK for the reasons of delayed diagnosis explained above. It is likely that the longer patients are symptomatic with FNS, the poorer their prognosis.[6] These strict criteria therefore exclude the very patients who need treatment and follow-up care most, and are likely to bias the results of this study, and limit its interpretability when applied to the broader population of patients with FNS.
Lastly, a single neurologist accounted for treatment of 90% of the patients in the intervention arm of the study. It is therefore conceivable that the (high) standard of care received by patients from this neurologist who had a specific interest in FNS reduced any additional benefit from further neurology follow-up appointments. Indeed 34% of the patients who were supposed to receive at least 2 follow-up appointments failed to do so either because they thought it was unnecessary, or because they did not attend the follow-up appointments. The generalizability of these findings must therefore be in question.
The authors suggest many useful ideas for future studies. However, the variability present in their approach to follow up appointments and the use of physiotherapy and psychotherapy, demonstrates that ultimately, individualized treatment and follow up plans remain the gold standard in this complex group of patients with competing biological, psychological and social factors relevant to their FNS. Furthermore, the management of new neurological symptoms, relapses of previous FNS and relevant neurological and other co-morbidities remains very important in order to prevent inappropriate re-referrals and investigations of patients.[7] For these reasons and those discussed above, we believe that neurological follow-up of these patients is often beneficial.
Reference list
1. Pleizier M, de Haan RJ, Vermeulen M. Management of patients with functional neurological symptoms: a single-centre randomised controlled trial. J Neurol Neurosurg Psychiatry. 2017;88(5):430-436.
2. Arie S. Why are Dutch GPs so much happier? BMJ. 2015;351:h6870.
3. Gregory R, Nicholl D, Lawrence J, et al. Association of British Neurologists (ABN) 2017 Acute Neurology Survey. March 2017.
4. Coebergh JA, Wren DR, Mumford CJ. ‘Undiagnosing’ neurological disease: how to do it, and when not to. Practical Neurology. 2014;14:436-439.
5. Couprie W, Wijdicks EF, Rooijmans HG, et al. Outcome in conversion disorder: a follow up study. J Neurol Neurosurg Psychiatry. 1995;58(6):750-2.
6. Gelauff J, Stone J, Edwards M, et al. The prognosis of functional (psychogenic) motor symptoms: a systematic review. J Neurol Neurosurg Psychiatry. 2014;85(2):220-6.
7. Crimlisk HL, Bhatia KP, Cope H, et al. Patterns of referral in patients with medically unexplained motor symptoms. J Psychosom Res. 2000;49(3):217-9.
We agree that an evaluation of the total cerebrovascular disease
(CeVD) burden is important to understand the effect of brain structural
abnormalities on clinical outcomes such as cognitive impairment and
neuropsychiatric disorders. Recently, integrated measures of total brain
MRI burden have been employed to understand neuropathological changes in
elderly. However, global CeVD burden may not be best measured by the
sim...
We agree that an evaluation of the total cerebrovascular disease
(CeVD) burden is important to understand the effect of brain structural
abnormalities on clinical outcomes such as cognitive impairment and
neuropsychiatric disorders. Recently, integrated measures of total brain
MRI burden have been employed to understand neuropathological changes in
elderly. However, global CeVD burden may not be best measured by the
simple ordinal addition of individual markers, as not all MRI markers
contribute equally to clinical outcomes. Hence we have argued that it is
essential to take into consideration differential weighting of individual
MRI markers when constructing a composite scale. In a previously published
paper (Xu et al, 2015), a weighted composite score of CeVD encompassing
both small vessel and large vessel disease markers was constructed and its
association with cognitive function was reported in a clinic population.
This scale was subsequently validated in a community sample and found
useful in differentiating between elderly at various clinical and
preclinical stages of dementia (Xu et al, 2016). We are currently
examining whether such associations are also found with global
neuropsychiatric burden and individual neuropsychiatric symptoms.
Reference:
1. Xu X, Hilal S, Collinson SL, Yi Chong EJ, Ikram MK,
Venketasubramanian N, Chen CLH (2015). Association of magnetic resonance
imaging markers of cerebrovascular disease burden and cognition. Stroke
46: 2808-2814
2. Xu X, Hilal S, Collinson SL, Chan QL, Chong EJY, Ikram MK,
Venketasubramanian N, Cheng CY, Wong TY, Chen C(2016). Validation of the
total cerebrovascular disease burden scale in a community sample. Journal
of Alzheimer's Disease 52:1021-1028
Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is an
autosomal dominant disorder caused by the mutations of the transthyretin
(TTR) gene. The mutant amyloidogenic TTR protein causes systemic
accumulation of amyloid fibrils that result in organ dysfunction [1]. Over
100 mutations in TTR gene are associated with the disease but still, the
first identified Val30Met mutation make up 50% of the cases worldwide....
Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is an
autosomal dominant disorder caused by the mutations of the transthyretin
(TTR) gene. The mutant amyloidogenic TTR protein causes systemic
accumulation of amyloid fibrils that result in organ dysfunction [1]. Over
100 mutations in TTR gene are associated with the disease but still, the
first identified Val30Met mutation make up 50% of the cases worldwide. In
the three main regions in which TTR-FAP is endemic (Portugal, Sweden and
Japan), the Val30Met mutation is the predominant genetic cause. However,
in non-endemic regions genetic features are more heterogeneous [2].
Clinical presentation is highly variable due to the interplay between
several factors consisting of genotype, geographical origin of the
patient, regional variation, penetrance of gene mutation and age at onset
of symptoms [2]. Length dependent axonal sensory-motor and autonomic
polyneuropathy is the hallmark feature of TTR-FAP hence, lower limb
sensory symptoms are generally the initial manifestations. Yet, Koike et
al reported that 5 of 50 patients presented with upper limb sensory
symptoms [3]. Herein, we describe a patient with Val30Met mutation
presented with asymmetrical upper limb symptoms which was not previously
reported in non-endemic regions. A 66-year-old male patient was admitted
with 3-year history of progressive numbness and pain in right hand. He
progressively deteriorated and his symptoms have spread to his left hand
in several months. He was diagnosed as bilateral carpal tunnel syndrome
and underwent bilateral surgical carpal tunnel ligament release. However,
he gradually worsened with tingling and numbness spreading to his forearms
followed by weakness in both hands without any significant lower limb
symptoms. He has had recurrent constipation, orthostatism and impotence,
which are suggestive of autonomic involvement, for three years. Two years
after the onset of the upper limb symptoms he developed numbness in
footpad, followed by pain and weakness in both legs. He was diagnosed
chronic inflammatory demyelinating polyneuropathy two years ago and
treated with prednisolone for six months. His past medical history was
significant for systemic hypertension and a myocardial infarction four
years prior. His grandfather, father and uncle had died from unknown
cardiac cause. In his initial examination, he had bilateral miosis, distal
muscle weakness predominantly in upper and left-side with absent deep
tendon reflexes, stocking and glove type hypoaesthesia and hypoalgesia,
diminished vibration sensation. Nerve conduction studies revealed a
demyelinating sensory and motor polyneuropathy syndrome accompanied by the
signs of axonal loss. These findings were accompanied by sympathetic
autonomic involvement. His cerebrospinal fluid (CSF) examination revealed
increased protein level (75 mg/dl) with normal cytological examination.
Urinalysis results showed microalbuminuria but urinary tract
ultrasonography was normal. Because of the positive family history of
unknown cardiac deaths, echocardiograpy was performed which revealed
secondary changes in the myocardium associated with amyloid deposition.
His cardiac magnetic resonance imaging results correlated with the
findings of echocardiogram. In his rhythm holter monitoring, baseline
rhythm was sinus with the average heart rate of 62/min (lowest heart rate:
47/min, highest heart rate: 78/min). No signs of arrythmia or conduction
blocks were detected. With those findings, we assumed that the patient had
amyloid associated neuropathy. Minor salivary gland biopsy was performed
and amyloid infiltration of the blood vessel wall and periductal field was
observed. Molecular analysis of TTR gene revealed heterozygous Val30Met
(c.148G>A) mutation in exon 2. Tafamidis 20 mg/day treatment was
initiated right after the patient was diagnosed. TTR-FAP is a
multisystemic and increasingly popular disease but still very difficult to
recognize especially in non-endemic regions. Various clinic presentations,
negative family history and the clinicians' lack of awareness are most
common causes of misdiagnosis. Upper limb onset axonal polyneuropathy is a
rare presentation in general practice and was not reported in TTR-FAP
patients in non-endemic regions [4]. Based on the natural course of the
disease, a duration of 4 to 5 years is expected before the upper limb
symptoms would start [5]. On the other hand, in a previous analysis of
late-onset cases with Val30Met mutation, 10% of the patients had upper
limb symptoms as the initial presentation. Among those patients, the mean
age at upper limb onset was 66.3 ? 5.8 whereas lower limb symptoms occured
at 66.5 ? 6.2 years of age. Although age at disease onset was nearly
similar in our case, duration between the upper limb and the lower limb
symptoms was slightly longer than the latter report. In conclusion, we
emphasize the heterogenous clinical presentation of late -onset FAP in non
-endemic regions. Careful examination and clinical suspicion is mandatory
for reducing the misdiagnosis of the atypical cases.
References
1. Andrade, C., A peculiar form of peripheral neuropathy; familiar
atypical generalized amyloidosis with special involvement of the
peripheral nerves. Brain, 1952. 75(3): p. 408-27.
2. Parman, Y., et al., Sixty years of transthyretin familial amyloid
polyneuropathy (TTR-FAP) in Europe: where are we now? A European network
approach to defining the epidemiology and management patterns for TTR-FAP.
Curr Opin Neurol, 2016. 29 Suppl 1: p. S3-13. 3.
3. Koike, H., et al., Natural history of transthyretin Val30Met
familial amyloid polyneuropathy: analysis of late-onset cases from non-
endemic areas. J Neurol Neurosurg Psychiatry, 2012. 83(2): p. 152-8. 4.
4. Durmus-Tekce, H., et al., Genotypic and phenotypic presentation of
transthyretin-related familial amyloid polyneuropathy (TTR-FAP) in Turkey.
Neuromuscul Disord, 2016. 26(7): p. 441-6. 5.
5. Conceicao, I., et al., "Red-flag" symptom clusters in
transthyretin familial amyloid polyneuropathy. J Peripher Nerv Syst, 2016.
21(1): p. 5- 9.
In a study published in J Neurol Neurosurg Psychiatry, Xu et al.1
aimed to investigate the relation between microbleeds (CMBs) and
Neuropsychiatric symptoms (NPS) in an elderly population, through a cross-
sectional study related to 802 participants. Interestingly, they found a
statistically significant increment of the incidence of depression, with
the presence of multiple CMBs, in particular lobar CMBs. This finding is...
In a study published in J Neurol Neurosurg Psychiatry, Xu et al.1
aimed to investigate the relation between microbleeds (CMBs) and
Neuropsychiatric symptoms (NPS) in an elderly population, through a cross-
sectional study related to 802 participants. Interestingly, they found a
statistically significant increment of the incidence of depression, with
the presence of multiple CMBs, in particular lobar CMBs. This finding is
in line with the previous research by Tang et al..2 However, a recent
study by Zhang et al.3 did not find the similar increment trend in deep
CMBs in patients with post-stroke depression, indicating that the presence
of lobar CMBs, not deep CMBs, was a potential predictor maker of
depression. While CMBs is one of the MRI biomarkers of cerebral small
vessel disease (cSVD) and was often accompanied by other cSVD-related
brain changes, such as lacunar infarcts, white matter lesions, and
enlarged perivascular spaces.
The available evidence suggests that cSVD was a principal determinant
in the pathogenesis and development of post-stroke depression,4 and
depression in patients with a prevalence of cerebrovascular disease burden
may be related more to cumulative vascular pathology than to the location
and severity of a single risk factor. Investigating the role of a total
MRI burden of cSVD in its pathogenesis may help to understand this disease
better. As the previously mentioned, Zhang et al. found that higher total
MRI burden of cSVD was an independent predictor of depression, even
without detecting an apparent association between deep CMBs and
depression. Similar to the study by Zhang et al., a recent research
investigated total MRI burden of cSVD in cerebral amyloid angiopathy
(CAA), in univariable analysis, total cSVD score was associated with the
presence of CAA-related changes on pathologic analysis and CAA
presentation with ICH, but none of the different MRI markers comprising
the score were individually linked to vasculopathic changes in univariable
or multivariable logistic regression analyses.5 These suggest that an
assessment of total MRI burden of cSVD has several potential advantages
because it avoids overreliance on any one individual marker of small
vessel disease.5 Hence, a complete evaluation of the total MRI burden of
cSVD may be important to understand the effect of cSVD on clinical
outcomes, such as depression.
Conflict of Interest Disclosures: None.
Reference:
1. Xu X, Chan QL, Hilal S, et al. Cerebral microbleeds and
neuropsychiatric symptoms in an elderly Asian cohort. Journal of
neurology, neurosurgery, and psychiatry 2017;88(1):7-11. doi: 10.1136/jnnp
-2016-313271
2. Tang WK, Chen Y, Liang H, et al. Cerebral microbleeds as a predictor of
1-year outcome of poststroke depression. Stroke; a journal of cerebral
circulation 2014;45(1):77-81. doi: 10.1161/STROKEAHA.113.002686
3. Zhang X, Tang Y, Xie Y, et al. Total magnetic resonance imaging burden
of cerebral small-vessel disease is associated with post-stroke depression
in patients with acute lacunar stroke. Eur J Neurol 2016 doi:
10.1111/ene.13213
4. Pavlovic AM, Pekmezovic T, Zidverc Trajkovic J, et al. Baseline
characteristic of patients presenting with lacunar stroke and cerebral
small vessel disease may predict future development of depression. Int J
Geriatr Psychiatry 2016;31(1):58-65. doi: 10.1002/gps.4289
5. Charidimou A, Martinez-Ramirez S, Reijmer YD, et al. Total Magnetic
Resonance Imaging Burden of Small Vessel Disease in Cerebral Amyloid
Angiopathy: An Imaging-Pathologic Study of Concept Validation. JAMA
neurology 2016;73(8):994-1001. doi: 10.1001/jamaneurol.2016.0832
We read with interest the findings and recommendations by the
authors. (1)
Cerebrovascular disease accounts for the increasing burden of
seizures and epilepsy in people over the age of 65 years. The distinction
between acute and remote symptomatic seizures is highly relevant with
implications both for prognosis and clinical management. Acute
symptomatic seizures (ASS) following a cerebrovascular event are def...
We read with interest the findings and recommendations by the
authors. (1)
Cerebrovascular disease accounts for the increasing burden of
seizures and epilepsy in people over the age of 65 years. The distinction
between acute and remote symptomatic seizures is highly relevant with
implications both for prognosis and clinical management. Acute
symptomatic seizures (ASS) following a cerebrovascular event are defined
as seizures that occur within 7 days of the ictus while remote symptomatic
seizures (RSS) occur out with this time frame. (2) ASS occur in around 6%
of acute cerebrovascular events and are more likely in elderly patients,
in those with large strokes, stroke involving the cortex or multiple
vascular territories, cardioembolic events, and haemorrhagic stroke. (3)
Data from the Rochester Epidemiology Project showed a risk for subsequent
seizures at 10 years of 33% for ASS, (4) similar to the 28% at 8 years in
the Leung Study. Both fall well below the 2014 ILAE operational definition
of epilepsy - an enduring predisposition of the brain to generate
seizures, defined as a probability of further seizures of at least 60%
over the next 10 years. In contrast, following a RSS the 10year risk of
further seizures is 71.5%. (4) Thus a diagnosis of epilepsy is not
justified for ASS in the context of stroke.
A decision to commence treatment with anti-epileptic drugs (AEDs)
should not be taken lightly; AEDs are commonly implicated in adverse drug
reactions, and those with a new brain insult may be particularly
susceptible to the mood and cognitive side effects, potentially
interfering with rehabilitation. AEDs have known effects on bone health,
together with an increased risk of drug interactions in patients who
already take numerous drugs to address their many comorbidities, and
economic and psychosocial impact. (5)
While short-term treatment of frequent seizures and status
epilepticus occurring within seven days of an acute stroke is appropriate,
the overwhelming evidence is that beyond one month there is no benefit
from treatment with AEDs. Data from the Rochester Epidemiology Project
showed that patients with ASS have a higher mortality during the first 30
days compared to subjects with RSS. (4) This is obviously related to the
severity of the underlying stroke but can justify the treatment of ASS in
order to minimize the additional contribution to mortality and morbidity
due to seizures. However, any recommendation for long-term treatment with
antiepileptic drugs beyond a period of a few weeks is against the
available evidence. For this reason treatment for four years, as
recommended by Leung et al (2016), risks unnecessary exposure of these
patients to medication they may not need for many years.
References:
1. Leung T, Leung H, Soo YOY, Mok VCT, Wong KS. The prognosis of acute
symptomatic seizures after ischaemic stroke. J Neurol Neurosurg
Psychiatry. 2016 Jan 27;
2. Beghi E, Carpio A, Forsgren L, Hesdorffer DC, Malmgren K, Sander JW,
et al. Recommendation for a definition of acute symptomatic seizure.
Epilepsia. 2010 Apr;51(4):671-5.
3. Leone MA, Tonini MC, Bogliun G, Gionco M, Tassinari T, Bottacchi E, et
al. Risk factors for a first epileptic seizure after stroke: a case
control study. J Neurol Sci. 2009 Feb 15;277(1-2):138-42.
4. Hesdorffer DC, Benn EKT, Cascino GD, Hauser WA. Is a first acute
symptomatic seizure epilepsy? Mortality and risk for recurrent seizure.
Epilepsia. 2009 May;50(5):1102-8.
5. Mula M, Cock HR. More than seizures: improving the lives of people
with refractory epilepsy. Eur J Neurol. 2015 Jan;22(1):24-30.
Roalf et al. describe a short form of the Montreal Cognitive
Assessment (s-MOCA) comprising 8 items (score range 0-16) from the
original MoCA.
Data from a historical cohort administered the MoCA (n = 150)1 were
examined to extract s-MoCA scores. There was high correlation between s-
MoCA scores and MoCA and MMSE scores (0.94, 0.80 respectively).
Roalf et al. describe a short form of the Montreal Cognitive
Assessment (s-MOCA) comprising 8 items (score range 0-16) from the
original MoCA.
Data from a historical cohort administered the MoCA (n = 150)1 were
examined to extract s-MoCA scores. There was high correlation between s-
MoCA scores and MoCA and MMSE scores (0.94, 0.80 respectively).
s-MoCA scores differed significantly (null hypothesis rejected)
between dementia and mild cognitive impairment (MCI), and between MCI (t =
2.6, p = 0.01) and subjective memory complaint (SMC; t = 6.6, p <
0.001).
Using the specified s-MoCA cutoff of <12/16, the test was very
sensitive (0.94) but not specific (0.25) for diagnosis of dementia versus
MCI, with a better balance for diagnosis of MCI versus SMC (sensitivity
0.75, specificity 0.66).
Effect sizes (Cohen's d) were medium for diagnosis of dementia versus
MCI (0.65) but large (1.19) for diagnosis of MCI versus SMC. All outcome
measures were similar to those for the MoCA.
This retrospective study suggests s-MoCA has utility as a cognitive
screening instrument for diagnosis of dementia and MCI in a dedicated
cognitive disorders clinic. Validation of s-MoCA in a prospective cohort
from this clinic (n > 200) is now being examined.
Reference
1. Larner AJ. Screening utility of the Montreal Cognitive Assessment
(MoCA): in place of - or as well as - the MMSE? Int Psychogeriatr
2012;24:391-6.
In an editorial commentary accompanying a recent study on the
prevalence of apraxia in dementia patients [1], Bak emphasizes two facts:
1) research in cognitive neuroscience is contributing to increase the
awareness of a close relationship between cognitive and motor functions
and, by extension, cognitive and motor disorders in clinical populations;
2) despite so, the examination of motor functions in patients with
cogn...
In an editorial commentary accompanying a recent study on the
prevalence of apraxia in dementia patients [1], Bak emphasizes two facts:
1) research in cognitive neuroscience is contributing to increase the
awareness of a close relationship between cognitive and motor functions
and, by extension, cognitive and motor disorders in clinical populations;
2) despite so, the examination of motor functions in patients with
cognitive disorders is not part of the routine clinical evaluation.
Apraxia is a disorder in executing voluntary motor programming, in the
absence of deficits in primary motor or sensory processes, comprehension
of task instructions, object recognition or frontal inertia. Bak
identifies apraxia as the critical disorder to address in routine clinical
evaluation of patients with cognitive symptoms, as "it is exactly at the
intersection between both [movement and cognition]". In Bak's view, a
major obstacle to the improvement of clinical practice in this direction,
is the absolute lack of tests for apraxia, practical and fast to use as
part of routine evaluation. The Edinburgh Motor Assessment, in preparation
by Bak and colleagues, is thus introduced as the first tool to respond to
this urge.
We could not agree more with the importance of considering apraxia in the
routine clinical evaluation of cognitive functions in neurological
patients, including those with dementia. Apraxia is indeed a cognitive
deficit, affecting the higher-order mechanisms that govern purposeful
motor production.
However, if poverty or absence of tools is the problem, then we might not
have a problem. Researchers have long since recognized apraxia as a
cognitive disorder (with consequences on motor production). Moreover,
efforts have been made to offer handy, standardized tests of praxis
functions (e.g., the test TULIA [2]), based on models of apraxia, whose
anatomo-functional correlates have been extensively studied in brain-
damaged patients and in healthy individuals, with neuroimaging research. A
problem with most previous tests, evaluating gesture recognition,
identification and production in great detail, is the administration time,
usually so long as to advise their use in a post-screening phase (i.e.,
after the patient received a diagnosis of apraxia). Addressing this
problem, Tessari et al. [3] have developed STIMA (short test for ideomotor
apraxia), a standardized test for an accurate but quick diagnosis of
apraxia. The test, also usable for bedside screening, requires the patient
to imitate 36 gestures that form eight subscales. The test and each
individual subscale are accompanied by tables to correct raw-scores for
age and education, and convert raw-scores into equivalent scores (useful
for clinicians to estimate deficit severity) and percentiles (more often
used for diagnosis in research). Different subscales test for different
praxic impairments. In particular, STIMA emphasizes the distinctions
between: 1) imitation errors indicative of cortical damage (e.g., sequence
errors or unrecognizable gestures) versus subcortical damage (e.g.,
postural or timing errors); 2) producing distal (fingers/hand) versus
proximal (arm) components of gesture; 3) producing known gestures, which
recruits semantic structures in the left temporo-parietal cortex, versus
producing novel gestures, which relies on a bilateral cortical network, to
transform the visual input (the seen gesture) in a motor act. The
evaluation of novel gestures is also crucial to detect praxis deficits in
patients who can properly use objects and tools in their domestic context.
Evaluation of praxis solely based on execution or reports of daily
activities may leave those cases unnoticed. STIMA has been used and proven
sensitive to apraxic deficits in patients with stroke [4], as well as
neurodegenerative pathologies [5].
Our short (and non-exhaustive) overview of available standardized tests of
apraxia shows a scenario brighter than the total absence of suitable tools
depicted by Bak, and does justice to the numerous research teams in
cognitive neuropsychology and neuroscience, who have paid more attention
than Bak fears, to the clinical scopes of their activity and the
constraints of the clinical setting (i.e., time pressure).
Since the Edinburgh Motor Assessment by Bak et al. comes after recent and
less recent attempts to provide clinicians with a fast and accurate test
of apraxia, one may ask: do we really need this new tool? Perhaps, the
Edinburgh Motor Assessment introduces features that make it more suitable
to dementia patients, than other tests; or it relates to a model of
apraxia, not represented in the other tests. Presenting the Edinburgh
Motor Assessment as the first step toward an apraxia test for clinical
practice precludes the possibility to clarify those or other potentially
important aspects of that test. Considering its relation to extant tools
rather appears as a good method to provide clear indications about which
tool one (e.g., a clinician) should select in which case. This may help
reducing the noise in the exchange between researchers and clinical
practitioners as well as within our research field.
References
1. Ahmed S, Baker I, Thompson S et al. Utility of testing for apraxia
and associated features in dementia. J Neurol Neurosurg Psychiatry 2016;
doi:10.1136/jnnp-2015-312945
2. Vanbellingen T, Kersten B, Van Hemelrijk B et al. Comprehensive
assessment of gesture production: a new test of upper limb apraxia
(TULIA). Eur J Neurol 2010;17:59-66.
3. Tessari A, Toraldo A, Lunardelli A, et al. STIMA: a short
screening test for ideo-motor apraxia, selective for action meaning and
bodily district. Neurol Sci 2015;36: 977-984.
4. Mengotti P, Corradi-Dell'Acqua C, Negri GA, et al. Selective
imitation impairments differentially interact with language processing.
Brain 2013;136:2602-2618
5. Papeo L, Cecchetto C, Mazzon G et al. The processing of actions
and action-words in amyotrophic lateral sclerosis patients. Cortex 2015;
64:136-147.
We thank dr. Coebergh and colleagues for their interest in our study. We agree that(a) there are many differences between the health care systems of the UK and the Netherlands, (b) the results of our study do not apply to excluded patients, and (c) the management of new neurological symptoms, relapses of previous FNS and relevant neurological and other co-morbidities remain very important in order to prevent inappropriate re-referrals and investigations of patients. However, in the absence of sound evidence from appropriate clinical studies,we disagree with the authors’ conclusion that neurological follow-up of these patients is often beneficial.
We wish to emphasize that in our study, firstly a neurologist established the diagnosis and briefly explained the diagnosis to the patient. Secondly, the first neurologist referred the patient to a specially trained second neurologist, who scheduled half an hour to discuss the diagnosis with the patient. This approach is clearly different from immediate referral to a GP after the diagnosis.
Does Cerebellar Atrophy in Neurodegeneration?
Li-Qin Sheng1, Ping-Lei Pan2
1 Department of Neurology, Traditional Chinese Medicine Hospital of Kunshan, Kunshan, PR China
2 Department of Neurology, Affiliated Yancheng Hospital, School of Medicine, Southeast University, Yancheng, PR China
Correspondence:
Show MorePingLei Pan, Department of Neurology, Affiliated Yancheng Hospital, School of Medicine, Southeast University, West Xindu Road 2#, Yancheng, Jiangsu Province, 224001, PR China. E-mail: panpinglei@163.com, Telephone: +8618361146977
Coordinate-based meta-analysis is a powerful way for neuroimaging studies to identify the most consistent and replicable differences in brain activity or structure in neurodegenerative disorders. In their JNNP publication, Gellersen et al 1 conducted coordinate-based meta-analyses of 54 voxel-based morphometry (VBM) studies in Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), behavioral variant frontotemporal dementia (bvFTD), amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). In this study, they solely focused on cerebellar grey matter (GM) atrophy.1 Marked cerebellar atrophy in AD, ALS, bvFTD, PSP and MSA, but not in PD or HD, was identified in the meta-analyses.1
These findings are of interest.1 However, the procedure of the meta-analyses had a major limitation. Coordin...
In our previous meta-analysis of cerebellar atrophy in seven major neurodegenerative conditions (Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Huntington’s disease (HD), Parkinson’s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP)) we investigated studies that reported grey matter (GM) loss in the cerebellum [1]. Consistent regions of atrophy were found in AD, ALS, FTD, MSA, and PSP but not HD or PD. In their comment on our meta-analysis, Sheng and Pan have argued that our method of selectively investigating studies that found cerebellar atrophy, rather than adopting a whole-brain approach, is “not optimal in a coordinate-based meta-analysis” [2]. They further cite previous whole-brain meta-analyses that did not identify clusters of cerebellar grey matter loss in patients [3-6].
Show MoreHere, we argue that our approach was justified given our aim, which was to focus on cases where cerebellar atrophy was found in the respective disease groups in order to determine 1) if such atrophy followed a consistent, robust pattern, and 2) if atrophy patterns were disease-specific or generic, where possible relating them to symptomatology.
There are several reasons why we chose to focus on the cerebellum rather than adopting a whole-brain approach. First, the cerebellum is hardly a “region of interest” in the classical sense given its marked heterogeneity in terms of function and connectivity as we...
It is good to see that trials are being done to answer the critical question of how best to provide care for those patients with functional neurological symptoms (FNS). The research paper, ‘Management of patients with functional neurological symptoms: a single-centre randomised controlled trial’, by Pleizier, de Haan and Vermeulen, randomizes outpatients with functional neurological symptoms after diagnosis, to either two outpatient appointments with a neurologist, or referral back to a GP. Intriguingly, it finds no difference in outcome, that is quality of life scores, between the two groups.[1] While this study attempts to address an important question, namely the role of the neurologist in the care of patients with functional neurological disorders, we feel it has a number of problems that limit its generalizability, particularly to UK neurology practice.
Show MoreThe Netherlands is a country that compared to the UK, has approximately four times as many neurologists per head of the population, and many more GPs with higher levels of job satisfaction,[2] and often have mental health nurse support in the practice itself. Neurology outpatient waiting times are shorter in the Netherlands, and in-patient neurology review happens routinely and is quicker, unlike in the UK where it may not occur at all.[3] Because of this lack of prompt neurological review in the UK, it is common for patients to receive erroneous diagnoses, often necessitating an “undiagnosis” at the eventual neu...
We agree that an evaluation of the total cerebrovascular disease (CeVD) burden is important to understand the effect of brain structural abnormalities on clinical outcomes such as cognitive impairment and neuropsychiatric disorders. Recently, integrated measures of total brain MRI burden have been employed to understand neuropathological changes in elderly. However, global CeVD burden may not be best measured by the sim...
Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disorder caused by the mutations of the transthyretin (TTR) gene. The mutant amyloidogenic TTR protein causes systemic accumulation of amyloid fibrils that result in organ dysfunction [1]. Over 100 mutations in TTR gene are associated with the disease but still, the first identified Val30Met mutation make up 50% of the cases worldwide....
In a study published in J Neurol Neurosurg Psychiatry, Xu et al.1 aimed to investigate the relation between microbleeds (CMBs) and Neuropsychiatric symptoms (NPS) in an elderly population, through a cross- sectional study related to 802 participants. Interestingly, they found a statistically significant increment of the incidence of depression, with the presence of multiple CMBs, in particular lobar CMBs. This finding is...
We read with interest the findings and recommendations by the authors. (1)
Cerebrovascular disease accounts for the increasing burden of seizures and epilepsy in people over the age of 65 years. The distinction between acute and remote symptomatic seizures is highly relevant with implications both for prognosis and clinical management. Acute symptomatic seizures (ASS) following a cerebrovascular event are def...
Roalf et al. describe a short form of the Montreal Cognitive Assessment (s-MOCA) comprising 8 items (score range 0-16) from the original MoCA.
Data from a historical cohort administered the MoCA (n = 150)1 were examined to extract s-MoCA scores. There was high correlation between s- MoCA scores and MoCA and MMSE scores (0.94, 0.80 respectively).
s-MoCA scores differed significantly (null hypothesis r...
In an editorial commentary accompanying a recent study on the prevalence of apraxia in dementia patients [1], Bak emphasizes two facts: 1) research in cognitive neuroscience is contributing to increase the awareness of a close relationship between cognitive and motor functions and, by extension, cognitive and motor disorders in clinical populations; 2) despite so, the examination of motor functions in patients with cogn...
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