I agree with Dhonde et al. (1) that a pair of humble 20 dioptre lens spectacle is often sufficient and less cumbersome than Frenzel glasses for routine bedside use at acute neurology and emergency wards. I have been using such glasses for more than 10 years to help distinguish peripheral from central nystagmus. Video 1 shows a lady with acute left vestibular neuronitis. Her right beating primary position nystagmus is more pronounced when visual fixation is removed using above-mentioned spectacles. Another trick is to ask the patient to gently shut the eye lids, Video 2. Some patients, like this man with acute left vestibular neuronitis, do have thin enough eyelids to discern the enhancement of nystagmus from the removal of visual fixation.
Reference:
1. Dhonde P, Khadilkar S. Frenzel glasses: an affordable alternative. Pract Neurol. 2020 Dec;20(6):504.
Legend for video:
a. VIDEO1-Peripheral nystagmus, more obvious with removal of visual fixation using modified Frenzel glasses: https://cloud.degoo.com/share/IKZ3Xj6YlnbMZ1Xe16ui0A
To address your first point, we did not carry out nerve conduction studies or electromyography. The patient was seen as a part of a hyperacute stroke service and we made the diagnosis within 48 hours of symptom onset. After finding an explanatory central lesion, we did not look further peripherally. It would seem to be highly unlikely the patient had developed a simultaneous acute stroke in a relevant area of cortex and peroneal nerve lesion. It is interesting you mention teaching medical students in your response - we teach our students about Occam's razor! As you will no doubt be aware, neurophysiology conducted this soon after symptom onset will be unlikely to contribute in any case, and we are not in the habit of recalling patients at a later date for additional investigations for purely academic value, and we are sure many would share our view this is not appropriate given the current pressure the NHS is under. A stroke diagnosis changes management in terms of secondary preventative medications, hypothetically diagnosing a co-existent compressive neuropathy does not add.
Secondly, we would argue that the location of this lesion does explain the neurological signs quite satisfactorily. As we know, the ankle dorsiflexors are in fact located in the anterior compartment of the lower leg, just below the knee and not actually in the foot itself. Furthermore, there is likely to be considerable individual var...
To address your first point, we did not carry out nerve conduction studies or electromyography. The patient was seen as a part of a hyperacute stroke service and we made the diagnosis within 48 hours of symptom onset. After finding an explanatory central lesion, we did not look further peripherally. It would seem to be highly unlikely the patient had developed a simultaneous acute stroke in a relevant area of cortex and peroneal nerve lesion. It is interesting you mention teaching medical students in your response - we teach our students about Occam's razor! As you will no doubt be aware, neurophysiology conducted this soon after symptom onset will be unlikely to contribute in any case, and we are not in the habit of recalling patients at a later date for additional investigations for purely academic value, and we are sure many would share our view this is not appropriate given the current pressure the NHS is under. A stroke diagnosis changes management in terms of secondary preventative medications, hypothetically diagnosing a co-existent compressive neuropathy does not add.
Secondly, we would argue that the location of this lesion does explain the neurological signs quite satisfactorily. As we know, the ankle dorsiflexors are in fact located in the anterior compartment of the lower leg, just below the knee and not actually in the foot itself. Furthermore, there is likely to be considerable individual variation in precise cortical areas where individual muscles are represented - to quote Penfield's original paper from which the homunculus is derived - "we do not know what the architectural pattern is in any particular case and how much these boundaries may vary from individual to individual", indeed they stated that between "different individuals the result will vary greatly so that any standardized chart which localizes the position of those points upon the cortex may be correct for one individual but not for all" (1).
Robin Fox and Laszlo Sztriha
Penfield W, Boldrey E. Somatic motor and sensory representation in the cortex of man as studied by electrical stimulation. Brain 1937; 60: 389-443
We read the above article (like all highly educational articles of Practical Neurology) with interest.
As the authors pointed out the clinical picture is highly suggestive of peroneal nerve lesion. There was no mention of NCS and EMG had been undertaken in this case. If NCS were carried out then it is prudent to stated that Nerve Conduction Studies excluded Common Peroneal nerve lesion, to make the case water tight and credible.
It is known that elderly would wake up with foot drop due to Peroneal nerve lesion and not necessarily indicate a stroke. In this case an ischaemic lesion was noted at the top of the motor strip and not in the depth of central sulcus where the foot is located. As the homunculus illustrates in Figure 2, the lesion is at the Knee area at best). Parasagittal meningiomas in the depth cause the foot weakness(also suggesting that the well-known ‘homunculus illustration is probably accurate’!) and we teach medical students practical neuroanatomy and localization using such examples. Thus it would be helpful for the paper to document all claims as accurately as possible.
Dr S Wimalaratna, Neurologist, Kettering General Hospital
Dr S Alagoda, Clinical Neurophysiologist, Musgrove Park Hospital, Taunton
Being a sufferer of Benign Fasciculation Syndrome (BFS) for more than a year, I read with great interest Professor Kiernan’s editorial (1), as well as Dr. Vercueil’s personal account of his encounter with the syndrome (2). I was relieved to see how much the “clinical course” of my case corresponded to that described by Professor Kiernan and Dr. Vercueil. They surfaced during a period of stress and sleep-deprivation, and has since kept going.
As Professor Kiernan writes, anything that increases central excitability can trigger fasciculations. This includes the fear that they form part of a prodrome to motor neuron disease (MND); a defining characteristic of Fasciculation Anxiety Syndrome in Clinicians (FASICS). Even though my diagnosis of BFS have been “confirmed” by an EMG and a neurologist, I still suffer from occasional episodes of FASICS exacerbations, surfacing like a recurrent nightmare according to its own inner logic. In other words, FASICS undoubtedly shares a quality with health anxiety, namely a jumbled relationship between symptoms and belief. The opening lines of H.P Lovecraft’s “The dreams in the witch house” captures this poetically; “Whether the dreams brought on the fever, or the fever brought on the dreams, Walter Gilman did not know”.
After years of working in hospitals you will have encountered some rare cases where the etiology of a disease have followed a non-standard pathway. These can unconsciously skew your wo...
Being a sufferer of Benign Fasciculation Syndrome (BFS) for more than a year, I read with great interest Professor Kiernan’s editorial (1), as well as Dr. Vercueil’s personal account of his encounter with the syndrome (2). I was relieved to see how much the “clinical course” of my case corresponded to that described by Professor Kiernan and Dr. Vercueil. They surfaced during a period of stress and sleep-deprivation, and has since kept going.
As Professor Kiernan writes, anything that increases central excitability can trigger fasciculations. This includes the fear that they form part of a prodrome to motor neuron disease (MND); a defining characteristic of Fasciculation Anxiety Syndrome in Clinicians (FASICS). Even though my diagnosis of BFS have been “confirmed” by an EMG and a neurologist, I still suffer from occasional episodes of FASICS exacerbations, surfacing like a recurrent nightmare according to its own inner logic. In other words, FASICS undoubtedly shares a quality with health anxiety, namely a jumbled relationship between symptoms and belief. The opening lines of H.P Lovecraft’s “The dreams in the witch house” captures this poetically; “Whether the dreams brought on the fever, or the fever brought on the dreams, Walter Gilman did not know”.
After years of working in hospitals you will have encountered some rare cases where the etiology of a disease have followed a non-standard pathway. These can unconsciously skew your worldview, making you focus on the “non-Gaussian” cases and off-the scale reports. When I first noticed my twitching, I frantically started researching Pubmed and discovered to my horror that there indeed were scattered reports of patients with apparently benign fasciculations progressing to MND (3). Having no background in neurology, I was unable to discern the details and, indeed, how rare these cases actually were. Nevertheless, they became the fuel of my bouts of FASICS. I gazed too long into the abyss and the abyss gazed back into me. I became the case reports.
The protagonist of Lovecraft’s story, Walter Gilman, is a student of non-euclidean geometry. He soon discovers that his rented room is constructed according to outlandish geometrical principles. Would he have noticed this without being knowledgeable in mathematics? His preoccupation with these geometrical patterns propels him into a strange and nightmarish dimension that eventually consumes him. Our background in medicine can sometimes lure us into such parallel dimensions when we misinterpret symptoms in ourselves.
Unlike Walter Gilman, I was not lost in a parallel world. My bouts of FASICS are now rare and short-lived, but it has been a long journey. Enduring such a journey can bring a reward. Like a booty brought back from a nightmare, my FASICS have also become a powerful reminder for me that it is all too easy to fall into the trap of Foucault’s “clinical gaze”, were the patient becomes a process, rather than an individual.
As a clinical pharmacist I often meet patients that are overly worried about adverse effects of drugs. Their anxieties are often caused by a uniformed reading of the package leaflet and internet research. The existence of rare, but dramatic side effects creates an illusory scientific foundation for their fears. When counselling these patients I try to make use of statistics, but now I know that such anxiety transcends the world of figures and a wider cognitive approach should be sought. Exiting a witch house built upon a strange “geometry” of “singularities” can be quite time-consuming.
Studies on long-term outcomes are invaluable in mapping the “Gaussian space” of BFS and FASICS (4, 5), but dealing with a non-Gaussian dimension requires the human touch described by Professor Kiernan, as well as reassuring personal testimonials like Dr. Vercueil’s. This is something other sufferers of FASICS can attest to, for example Dr. Mert Erogul in his excellent Guardian long-read “The perils of being your own doctor”. What finally made him realize he was not on the path to MND was the fact that his own neurologist also suffered from benign fasciculations (6). Being lost in a witch house of case reports, you need the “anti-case reports” to show you the way out.
References:
1. Kiernan MC. Fasciculation anxiety syndrome in clinicians: FASICS. Pract Neurol. 2020;20(6):433-4.
2. Vercueil L. FASICS: fasciculation anxiety syndrome in clinicians. Pract Neurol. 2020;20(6):514-5.
3. Singh V, Gibson J, McLean B, Boggild M, Silver N, White R. Fasciculations and cramps: how benign? Report of four cases progressing to ALS. J Neurol. 2011;258(4):573-8.
4. Blexrud MD, Windebank AJ, Daube JR. Long-term follow-up of 121 patients with benign fasciculations. Ann Neurol. 1993;34(4):622-5.
5. Simon NG, Kiernan MC. Fasciculation anxiety syndrome in clinicians. J Neurol. 2013;260(7):1743-7.
6. Erogul M. The perils of being your own doctor: The Guardian; 2016 [Available from: https://www.theguardian.com/news/2016/aug/04/perils-being-your-own-docto....
We read with great interest the recent article by Drs Page & Gaillard describing neuroradiology signs and their variable utility [1].
We recently attempted to bring science to the art of descriptive radiological signs by conducting a randomized controlled trial to assess the utility of these signs for medical student radiology education [2]. We found that ‘Metaphoric Signs’ (linking radiology resemblance to an object or concept which is not actually present in an image) increased descriptive and diagnostic ability as well as students’ lesson enjoyment, when compared to teaching with normal anatomy comparators.
The importance of diagnostic accuracy of commonly used signs was similarly emphasised in our discussion. In addition to being diagnostically accurate, the success of a metaphoric sign also relies on how well it resonates with each individual learner, based on their perception of the real-world similarity alluded to in the radiology image and their prior experiences[3,4]. This is aptly exemplified by Author FG’s stronger association of the pontine appearance in osmotic demyelination with a blockbuster sci-fi trilogy than classical mythology.
An interesting observation in our study was that several students used incorrect wording for the name of the signs yet identified the correct diagnosis. Students who correctly diagnosed agenesis of the corpus callosum from a coronal MRI image containing the ‘Moose head sign’ [5] varia...
We read with great interest the recent article by Drs Page & Gaillard describing neuroradiology signs and their variable utility [1].
We recently attempted to bring science to the art of descriptive radiological signs by conducting a randomized controlled trial to assess the utility of these signs for medical student radiology education [2]. We found that ‘Metaphoric Signs’ (linking radiology resemblance to an object or concept which is not actually present in an image) increased descriptive and diagnostic ability as well as students’ lesson enjoyment, when compared to teaching with normal anatomy comparators.
The importance of diagnostic accuracy of commonly used signs was similarly emphasised in our discussion. In addition to being diagnostically accurate, the success of a metaphoric sign also relies on how well it resonates with each individual learner, based on their perception of the real-world similarity alluded to in the radiology image and their prior experiences[3,4]. This is aptly exemplified by Author FG’s stronger association of the pontine appearance in osmotic demyelination with a blockbuster sci-fi trilogy than classical mythology.
An interesting observation in our study was that several students used incorrect wording for the name of the signs yet identified the correct diagnosis. Students who correctly diagnosed agenesis of the corpus callosum from a coronal MRI image containing the ‘Moose head sign’ [5] variably described a ‘Mule head’, ‘deer head’ and ‘antler head’ appearance. This may be explained by the wording of a sign having lesser importance for diagnosis than the strength of the metaphoric association identified by the learner between the radiological appearance and the real-world metaphoric resemblance, or ‘Pareidolia’.
Following on from this, we would suggest that the hoofed ruminant animal in Figure 2d of the paper by Page & Gaillard is actually stag deer (Subfamily: Cervinae, Genus: Cervus) rather than a Moose (Subfamily: Capreolinae, Genus: Alces). However, in our opinion, the coronal MRI provided (Figure 2c) appearance of agenesis of the corpus callosum truly does resemble a male deer (Stag) rather than a Moose! Therefore, the image provided may result in the strongest metaphoric association with the correct diagnosis in readers.
1. Page I, Gaillard F. Descriptive neuroradiology: beyond the hummingbird. Pract Neurol Published Online First: 27 August 2020. doi:10.1136/practneurol-2020-002526
2. Gibney B, Ghadir KH, Redmond CE et al. Pareidolia in Radiology Education: A Randomized Controlled Trial of Metaphoric Signs in Medical Student Teaching. Acad Radiol. 2020 Sep 17:S1076-6332(20)30498-0. doi: 10.1016/j.acra.2020.08.017.
3. Baker SR, Partyka L. Relative Importance of Metaphor in Radiology versus Other Medical Specialties. RadioGraphics. 2012;32:235–40. doi:10.1148/rg.321115721
4. Lakoff G. The contemporary theory of metaphor. Metaphor and Thought. 1993;:202–51. doi:10.1017/cbo9781139173865.013
5. Cherian EV, Shenoy KV, Bukelo MJ, et al. Racing car brings tear drops in the moose. BMJ Case Rep 2013;2013. doi:10.1136/bcr-2012-008165
We greatly enjoyed the excellent recent review on the diagnosis and management of primary lateral sclerosis (PLS). Turner and Talbot emphasize the importance of controlling spasticity as the most troublesome symptom, which is often associated with pain, discomfort and physical disability [1].
As the authors point out, the current standard of care (baclofen, tizanidine, benzodiazepines and botulinum toxin) is frequently complicated by side effects, difficulties in titration and a lack of well controlled clinical studies [2]. We were thus surprised that the authors omitted the option of medicinal cannabis from the discussion of this very important topic.
A study by Riva and colleagues offers clear evidence on the efficacy of the cannabinoid preparation Nabiximol for the control of spasticity in ALS and PLS patients [3], which is further supported by Meyer and colleagues providing compelling real world evidence of this effect [4].
The THC:CBD oromucosal spray (nabioximols, brand name Sativex) became approved in European Union countries in 2010. Although only approved for people with moderate to severe spasticity in multiple sclerosis, who have not responded adequately to other anti-spasticity regimes, THC:CBD is increasingly being used off-label for spasticity in patients with motor neuron diseases. In addition, the patients themselves have self-medicated with recreational cannabis for many years [5].
The multicenter, double-blind,...
We greatly enjoyed the excellent recent review on the diagnosis and management of primary lateral sclerosis (PLS). Turner and Talbot emphasize the importance of controlling spasticity as the most troublesome symptom, which is often associated with pain, discomfort and physical disability [1].
As the authors point out, the current standard of care (baclofen, tizanidine, benzodiazepines and botulinum toxin) is frequently complicated by side effects, difficulties in titration and a lack of well controlled clinical studies [2]. We were thus surprised that the authors omitted the option of medicinal cannabis from the discussion of this very important topic.
A study by Riva and colleagues offers clear evidence on the efficacy of the cannabinoid preparation Nabiximol for the control of spasticity in ALS and PLS patients [3], which is further supported by Meyer and colleagues providing compelling real world evidence of this effect [4].
The THC:CBD oromucosal spray (nabioximols, brand name Sativex) became approved in European Union countries in 2010. Although only approved for people with moderate to severe spasticity in multiple sclerosis, who have not responded adequately to other anti-spasticity regimes, THC:CBD is increasingly being used off-label for spasticity in patients with motor neuron diseases. In addition, the patients themselves have self-medicated with recreational cannabis for many years [5].
The multicenter, double-blind, randomized, placebo-controlled, phase 2 CANALS trial, Riva et al. showed that nabiximols was not only safe and well tolerated in patients with ALS and PLS, but had a significant positive effect on spasticity reflected by significant improvements in scores on the Modified Ashworth Scale, and had an additional beneficial effect on spasticity-related pain [3]. Additionally, in a subsequent retrospective mono-centric real-world cohort of ALS patients, Meyer et al. showed recently that the nabiximols treatment satisfaction was high and dosing was titrated individually. Especially, patients with moderate to severe spasticity self-reported a strong recommendation rate in comparison to patients with mild spasticity [4]. Thus the available evidence on treatment of spasticity in MND with cannabis is superior to the classical options.
Both studies have influenced the clinical practice in our Motor Neuron Disease unit and to date our experience has borne out the expectations raised by the studies.
1 Turner MR, Talbot K. Primary lateral sclerosis: diagnosis and management. Pract Neurol 2020;:practneurol-2019-002300. doi:10.1136/practneurol-2019-002300
2 Ashworth NL, Satkunam LE, Deforge D. Treatment for spasticity in amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database of Systematic Reviews Published Online First: 15 February 2012. doi:10.1002/14651858.CD004156.pub4
3 Riva N, Mora G, Sorarù G, et al. Safety and efficacy of nabiximols on spasticity symptoms in patients with motor neuron disease (CANALS): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial. The Lancet Neurology 2019;18:155–64. doi:10.1016/S1474-4422(18)30406-X
4 Meyer T, Funke A, Münch C, et al. Real world experience of patients with amyotrophic lateral sclerosis (ALS) in the treatment of spasticity using tetrahydrocannabinol:cannabidiol (THC:CBD). BMC Neurol 2019;19:222. doi:10.1186/s12883-019-1443-y
5 Amtmann D, Weydt P, Johnson KL, et al. Survey of cannabis use in patients with amyotrophic lateral sclerosis. Am J Hosp Palliat Care 2004;21:95–104. doi:10.1177/104990910402100206
Competing interests: none
Acknowledgements: not applicable
Contributorship: SCG and PW conceived and drafted the letter, MTH edited
Funding info: not applicable
Ethical approval information: not applicable
Data sharing statement: not applicable
We thank Dr Weydt and colleagues for their interest in our review. We are aware of the subjective benefit of cannabinoids reported by some living with multiple sclerosis, and a trial of THC:CDB spray is also approved by the UK’s National Institute for Health & Care Excellence (NICE). The CANALS study mentioned, in which PLS patients were well represented (28% of treatment arm and 20% of placebo arm), was a Phase 2 study powered to consider safety and tolerability. Adverse events were reported in 76% of the treatment group versus 27% in the placebo group. A reduction in the clinician’s Modified Ashworth Spasticity scale score was noted, and in the patient’s numeric rating scale score for pain, but not their scores for spasm or spasticity. In the discussion, the authors note that muscle cramping was not alleviated in a prior randomised trial of THC in ALS (1). We agree with their call for further evaluation, through a Phase 3 study of the benefit of cannabinoids over the licensed therapies for spasticity outlined in our review.
Reference:
1. Weber M, Goldman B, Truniger S. Tetrahydrocannabinol (THC) for cramps in amyotrophic lateral sclerosis: a randomised, double-blind crossover trial. J Neurol Neurosurg Psychiatry. 2010 Oct;81(10):1135-40. doi: 10.1136/jnnp.2009.200642. PMID: 20498181.
It gives more discomfort than pleasure to comment on DaT scanning again but your editorial [1] prompted me to find out that the number of DaTscans carried out in England is increasing yearly, from 4550 in 2012/3 to 8840 in 2018/9. A trip to the dentist might have been wiser, my long-expressed opinion (based on the fundamental principles that let down 18FDopa PET) being that the DaTscan is a waste of time, radiation and money [2]. In brief it is a low resolution, inadequately sensitive, inadequately reproducible test with too many false negatives and little knowledge of confounding influences. The acronym SWEDD has, mercifully, been consigned to the dustbin[3] but we don’t have the neuropathological studies or large and long-term blinded follow-up studies, in patients and healthy individuals, despite the many tests and years since its commercial introduction, that would tell the true false positive and negative rate of the test. We can’t then confidently say how strongly a normal result argues against a clinical diagnosis of PD. Neurology is not the only specialty that uses DaTscan and indication-creep (good for the shareholder, bad for the taxpayer) means that it is also being used to distinguish Lewy Body Dementia from Alzheimer’s Dementia despite limited supportive data (4). It must also be remembered that the test measures biochemistry, not pathology; the statement in the case presentation [5] “a DaTscan was normal, with no evidence of degenerative Parkinsonism” is...
It gives more discomfort than pleasure to comment on DaT scanning again but your editorial [1] prompted me to find out that the number of DaTscans carried out in England is increasing yearly, from 4550 in 2012/3 to 8840 in 2018/9. A trip to the dentist might have been wiser, my long-expressed opinion (based on the fundamental principles that let down 18FDopa PET) being that the DaTscan is a waste of time, radiation and money [2]. In brief it is a low resolution, inadequately sensitive, inadequately reproducible test with too many false negatives and little knowledge of confounding influences. The acronym SWEDD has, mercifully, been consigned to the dustbin[3] but we don’t have the neuropathological studies or large and long-term blinded follow-up studies, in patients and healthy individuals, despite the many tests and years since its commercial introduction, that would tell the true false positive and negative rate of the test. We can’t then confidently say how strongly a normal result argues against a clinical diagnosis of PD. Neurology is not the only specialty that uses DaTscan and indication-creep (good for the shareholder, bad for the taxpayer) means that it is also being used to distinguish Lewy Body Dementia from Alzheimer’s Dementia despite limited supportive data (4). It must also be remembered that the test measures biochemistry, not pathology; the statement in the case presentation [5] “a DaTscan was normal, with no evidence of degenerative Parkinsonism” is a common but incorrect oversimplification. For drug-induced parkinsonism, is it my own oversimplification to ask why a drug that is biochemically producing parkinsonism doesn’t change the result of a biochemical test that is used to detect parkinsonism? Small studies with an unreliable test and heavy sales pitch encourage more indication-creep.
A practical neurologist’s approach is to ask if the outcome of a test will change what one does or advises and if a test can’t be trusted it shouldn’t be requested. I wonder if the £12M or more spent on the test in England in 2018 might have been more usefully used and whether the Scottish, known for their financial prudence, have a neologism for colleagues that request DaTscans?
References:
1. Araujo R, van Rumund A, Bloem BR. To scan or not to scan your Parkinson patient: that is the question! Pract Neurol 2019;19:462-4. doi: 10.1136/practneurol-2019-002225
2. Morrish PK. Controversies in Neuroimaging. in Factor SA and Weiner WJ eds. Parkinson’s disease; Diagnosis and Clinical Management. Demos Publishing (New York). 2008: 317-326
3. Erro R, Schneider SA, Stamelou M, et al. What do patients with scans without evidence of dopaminergic deficit (SWEDD) have? New evidence and continuing controversies. J Neurol Neurosurg Psychiatry 2016; 87: 319-323. doi: 10.1136/jnnp-2014-310256
4. McCleery J, Morgan S, Bradley KM et al. Dopamine transporter imaging for the diagnosis of dementia with Lewy bodies. Cochrane Database of Systematic Reviews 2015, Issue 1. Art. No.: CD010633. doi: 10.1002/14651858.CD010633.pub2
5. Wiblin I, Mitra D, Naomi W. An unusual cause of treatable parkinsonism. Pract Neurol 2019; 19; 518-20. doi: 10.1136/practneurol-2019-002339
Acknowledgement: Figures for 2018 DaTscan use kindly provided by Sheila M Dixon, Senior Analytical Manager, Performance Analysis Team, NHS England & NHS Improvement
With great interest, we read the review by Markus on personalising the secondary prevention approach to patients with stroke ¹, published in the most recent issue of Practical Neurology. Where we are presented with clinically useful and evidence-based advice for the etiological assessment of patients with acute ischemic stroke (AIS), focusing on lacunar stroke syndromes of a non-lacunar cause, and its appropriate therapeutic management. We consider the article of great importance: a must-read for all physicians who care for patients with AIS since etiological assessment is paramount to dictate the appropriate secondary prevention measures.
The author proposes using the TOAST classification (Trial of Organon 10172 in Acute Stroke Treatment), arguing that classification systems that prime clinical syndromes over pathophysiological mechanisms are less useful. Nevertheless, the author omitted one classification which–partially–resolves the issue: the ASCOD (Atherosclerosis, Small-vessel, Cardiac embolism, Other, Dissection) system ². A comprehensive classification, which allows for more than one aetiology, while giving a degree of a causal relationship to the presence of each category of disease (1 potential, 2 uncertain, 3 unlikely, 0 disease not detected) including incomplete assessment (9 insufficient work-up), while considering some clinical features.
The ASCOD approach permits the identification of patients with diseases that would have been left as indeterm...
With great interest, we read the review by Markus on personalising the secondary prevention approach to patients with stroke ¹, published in the most recent issue of Practical Neurology. Where we are presented with clinically useful and evidence-based advice for the etiological assessment of patients with acute ischemic stroke (AIS), focusing on lacunar stroke syndromes of a non-lacunar cause, and its appropriate therapeutic management. We consider the article of great importance: a must-read for all physicians who care for patients with AIS since etiological assessment is paramount to dictate the appropriate secondary prevention measures.
The author proposes using the TOAST classification (Trial of Organon 10172 in Acute Stroke Treatment), arguing that classification systems that prime clinical syndromes over pathophysiological mechanisms are less useful. Nevertheless, the author omitted one classification which–partially–resolves the issue: the ASCOD (Atherosclerosis, Small-vessel, Cardiac embolism, Other, Dissection) system ². A comprehensive classification, which allows for more than one aetiology, while giving a degree of a causal relationship to the presence of each category of disease (1 potential, 2 uncertain, 3 unlikely, 0 disease not detected) including incomplete assessment (9 insufficient work-up), while considering some clinical features.
The ASCOD approach permits the identification of patients with diseases that would have been left as indeterminate with other classification systems, thus increasing the risk of stroke because of inadequate secondary prevention. Comparisons with other classification systems have shown that ASCO (the predecessor of ASCOD) allows for more than one cause of stroke, with a larger proportion of atherosclerosis and lower of indeterminate and small vessel disease with the potential to magnify cardiac embolism thus leading to overtreatment ³, but with a recurrence risk strongly tied to aetiology regardless of the classification system used ⁴.
However, both of the above mentioned-comparisons have a flaw: they used ASCO as a dichotomic variable, which is not, and is precisely the advantage of ASCOD, that allows individualizing secondary prevention approaches for the most likely aetiology without discarding other possible etiologies, thus decreasing the proportion of indeterminate strokes facilitating inclusion for clinical trials ⁵. The relevance of considering multiple etiologies this has been demonstrated by studies like AMISTAD in which concurrent intra- and extracranial atherosclerosis increased the risk of major adverse cardiovascular events ⁶, and the secondary analysis of SOCRATES, which demonstrated ticagrelor to be superior to aspirin in patients with atherosclerosis regardless of causal link ⁷.
Bottom line, the critical issue is to assess patients with AIS to detect the most likely aetiology responsible for the stroke, without losing sight of possible comorbidities and regardless of the classification system used. In our Hospital, we use ASCOD since it allows neurology residents to consider all potential etiologies, but each centre should individualize to its specific needs.
References
1. Markus H. Personalising secondary prevention: different treatments for different strokes. Practical Neurology Published Online First: 04 September 2019 doi: 10.1136/practneurol-2018-002006
2. Amarenco P, Bogousslavsky J, Caplan LR, et al. The ASCOD phenotyping of ischemic stroke (Updated ASCO Phenotyping). Cerebrovasc Dis 2013;36(1):1-5. doi: 10.1159/000352050
3. Shang W, Liu J. Stroke subtype classification: a comparative study of ASCO and modified TOAST. J Neurol Sci 2012;314(1-2):66-70. doi: 10.1016/j.jns.2011.10.029
4. Arsava EM, Helenius J, Avery R, et al. Assessment of the Predictive Validity of Etiologic Stroke Classification. JAMA Neurol 2017;74(4):419-26. doi: 10.1001/jamaneurol.2016.5815
5. Sirimarco G, Lavallee PC, Labreuche J, et al. Overlap of diseases underlying ischemic stroke: the ASCOD phenotyping. Stroke 2013;44(9):2427-33. doi: 10.1161/STROKEAHA.113.001363
6. Hoshino T, Sissani L, Labreuche J, et al. Prevalence of Systemic Atherosclerosis Burdens and Overlapping Stroke Etiologies and Their Associations With Long-term Vascular Prognosis in Stroke With Intracranial Atherosclerotic Disease. JAMA Neurol 2018;75(2):203-11. doi: 10.1001/jamaneurol.2017.3960
7. Amarenco P, Albers GW, Denison H, et al. Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial. Lancet Neurol 2017;16(4):301-10. doi: 10.1016/S1474-4422(17)30038-8
Following the publication of the “UK consensus on pregnancy in multiple sclerosis: ABN guidelines” in January 2019, new data has become available and an update is required. Whilst these updates do not change the overall recommendations in the guidelines, they add information, which we feel all neurologists should be aware of in order to provide the highest quality of information to all women with MS considering pregnancy.
(1) Interferon beta preparations in pregnancy
In September 2019, the EMA Committee for Medicinal Products for Human Use (CHMP) recommended a label change for interferon beta-1a, peginterferon beta-1a and interferon beta-1b, i.e. Avonex, Betaferon, Extavia, Plegridy and Rebif, stating that they may be considered during pregnancy if clinically indicated, and can be used during breastfeeding [1]. This decision was based on data from interferon beta registries, national registries and post-marketing experience. However, data from exposure during second and third trimesters remains limited. The duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and it is likely that treatment was interrupted in many women when the pregnancy was detected and/or confirmed.
This supports the recommendation in the “UK consensus on pregnancy in multiple sclerosis: ABN guidelines” that these products are safe to be continued at least until...
Following the publication of the “UK consensus on pregnancy in multiple sclerosis: ABN guidelines” in January 2019, new data has become available and an update is required. Whilst these updates do not change the overall recommendations in the guidelines, they add information, which we feel all neurologists should be aware of in order to provide the highest quality of information to all women with MS considering pregnancy.
(1) Interferon beta preparations in pregnancy
In September 2019, the EMA Committee for Medicinal Products for Human Use (CHMP) recommended a label change for interferon beta-1a, peginterferon beta-1a and interferon beta-1b, i.e. Avonex, Betaferon, Extavia, Plegridy and Rebif, stating that they may be considered during pregnancy if clinically indicated, and can be used during breastfeeding [1]. This decision was based on data from interferon beta registries, national registries and post-marketing experience. However, data from exposure during second and third trimesters remains limited. The duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and it is likely that treatment was interrupted in many women when the pregnancy was detected and/or confirmed.
This supports the recommendation in the “UK consensus on pregnancy in multiple sclerosis: ABN guidelines” that these products are safe to be continued at least until conception, in addition to extending this advice such that women should be offered the choice of continuation during pregnancy.
(2) Fingolimod (Gilenya)
In September 2019, the MHRA issued an alert on the safety of fingolimod (Gilenya) in pregnancy [2] after data from international pregnancy registers demonstrated that exposure in pregnancy leads to an estimated additional two to three major congenital malformations per 100 livebirths compared with the general population (a two-fold increase). Reported malformations include congenital heart disease, such as tetralogy of Fallot, atrial and ventricular septal defects, and renal and musculoskeletal abnormalities [2].
If a woman of childbearing potential is started on fingolimod, the advice in the summary of product characteristics is that she must be informed of the risk of teratogenicity and provided with a patient reminder card. She must have a negative pregnancy test before receiving the first dose and at suitable intervals during treatment as appropriate. She should be regularly advised to use effective contraception during treatment and for at least two months after stopping it. Women should be advised that recurrence of disease activity, which can be substantial, has been reported in around a quarter of women after stopping fingolimod to get pregnant [4-6].
In November 2018, the license for fingolimod was extended to include its use in for children and young adults (10-17 years) with MS [3]. Due to limited treatment options in this group, fingolimod use in young women is anticipated to increase.
In our opinion, fingolimod is best avoided in women of childbearing age unless there is no other suitable treatment. Serious consideration should be given to proactively switching women of childbearing age who are taking fingolimod to an alternative DMD of at least similar efficacy well in advance of trying to conceive, and the possibility of unplanned pregnancy should be considered in all women of childbearing potential.
Work is ongoing to develop a UK MS Pregnancy Register; the above new information highlights the need for an independent register to inform practice.
Dr Ruth Dobson1,2* and Dr Peter Brex3; on behalf of all authors and the UK MS Pregnancy Register Steering Group
Acknowledgements
The following individuals and groups provided input into this update:
UK MS Pregnancy Register steering group (Dr David Rog, Dr Owen Pearson, Dr Katy Murray, Dr Stella Hughes, Dr Helen Ford, Dr Peter Brex and Dr Ruth Dobson)
UK consensus on pregnancy in multiple sclerosis: ABN guideline authors (Dr Catherine Nelson-Piercy, Dr Pooja Dassan, Megan Roberts, Prof Gavin GIovannoni)
Aoife Shields, Neuroscience Specialist Pharmacist
References
1. https://www.acnr.co.uk/2019/09/interferon-beta-treatments-receive-positi...
2. https://www.gov.uk/drug-safety-update/fingolimod-gilenya-increased-risk-...
3. https://www.ema.europa.eu/en/documents/product-information/gilenya-epar-...
4. Hemat S, Houtschens M, Vidal-Jordana A, et al. Disease activity during pregnancy after Fingolimod withdrawal due to planning a pregnancy in women with multiple sclerosis. Poster presented at: 70th American Academy of Neurology Annual Meeting; April 21–27, 2018; Los Angeles, CA.
5. Meinl I, Havla J, Hohlfeld R, Kümpfel T. Recurrence of disease activity during pregnancy after cessation of fingolimod in multiple sclerosis. Mult Scler 2018;24(7):991–914. doi:10.1177/ 1352458517731913.
6. Novi G, Ghezzi A, Pizzorno M, et al. Dramatic rebounds of MS during pregnancy following fingolimod withdrawal. Neurol Neuroimmunol Neuroinflamm 2017;4(5):e377. doi:10.1212/ NXI.0000000000000377.
I agree with Dhonde et al. (1) that a pair of humble 20 dioptre lens spectacle is often sufficient and less cumbersome than Frenzel glasses for routine bedside use at acute neurology and emergency wards. I have been using such glasses for more than 10 years to help distinguish peripheral from central nystagmus. Video 1 shows a lady with acute left vestibular neuronitis. Her right beating primary position nystagmus is more pronounced when visual fixation is removed using above-mentioned spectacles. Another trick is to ask the patient to gently shut the eye lids, Video 2. Some patients, like this man with acute left vestibular neuronitis, do have thin enough eyelids to discern the enhancement of nystagmus from the removal of visual fixation.
Reference:
1. Dhonde P, Khadilkar S. Frenzel glasses: an affordable alternative. Pract Neurol. 2020 Dec;20(6):504.
Legend for video:
a. VIDEO1-Peripheral nystagmus, more obvious with removal of visual fixation using modified Frenzel glasses: https://cloud.degoo.com/share/IKZ3Xj6YlnbMZ1Xe16ui0A
b. VIDEO2-Peripheral nystagmus, worse on eye closure: https://cloud.degoo.com/share/FyVfA144V6oHsULRgUOuIQ
Thank you for your interest in our case report.
To address your first point, we did not carry out nerve conduction studies or electromyography. The patient was seen as a part of a hyperacute stroke service and we made the diagnosis within 48 hours of symptom onset. After finding an explanatory central lesion, we did not look further peripherally. It would seem to be highly unlikely the patient had developed a simultaneous acute stroke in a relevant area of cortex and peroneal nerve lesion. It is interesting you mention teaching medical students in your response - we teach our students about Occam's razor! As you will no doubt be aware, neurophysiology conducted this soon after symptom onset will be unlikely to contribute in any case, and we are not in the habit of recalling patients at a later date for additional investigations for purely academic value, and we are sure many would share our view this is not appropriate given the current pressure the NHS is under. A stroke diagnosis changes management in terms of secondary preventative medications, hypothetically diagnosing a co-existent compressive neuropathy does not add.
Secondly, we would argue that the location of this lesion does explain the neurological signs quite satisfactorily. As we know, the ankle dorsiflexors are in fact located in the anterior compartment of the lower leg, just below the knee and not actually in the foot itself. Furthermore, there is likely to be considerable individual var...
Show MoreLetter to the editor; 14th February 2021
RE: Cortical foot
Fox R,Sztriha L. Pract Neurol 2021, 21:73-74
Dear Editors,
We read the above article (like all highly educational articles of Practical Neurology) with interest.
As the authors pointed out the clinical picture is highly suggestive of peroneal nerve lesion. There was no mention of NCS and EMG had been undertaken in this case. If NCS were carried out then it is prudent to stated that Nerve Conduction Studies excluded Common Peroneal nerve lesion, to make the case water tight and credible.
It is known that elderly would wake up with foot drop due to Peroneal nerve lesion and not necessarily indicate a stroke. In this case an ischaemic lesion was noted at the top of the motor strip and not in the depth of central sulcus where the foot is located. As the homunculus illustrates in Figure 2, the lesion is at the Knee area at best). Parasagittal meningiomas in the depth cause the foot weakness(also suggesting that the well-known ‘homunculus illustration is probably accurate’!) and we teach medical students practical neuroanatomy and localization using such examples. Thus it would be helpful for the paper to document all claims as accurately as possible.
Dr S Wimalaratna, Neurologist, Kettering General Hospital
Dr S Alagoda, Clinical Neurophysiologist, Musgrove Park Hospital, Taunton
To the Editors,
Being a sufferer of Benign Fasciculation Syndrome (BFS) for more than a year, I read with great interest Professor Kiernan’s editorial (1), as well as Dr. Vercueil’s personal account of his encounter with the syndrome (2). I was relieved to see how much the “clinical course” of my case corresponded to that described by Professor Kiernan and Dr. Vercueil. They surfaced during a period of stress and sleep-deprivation, and has since kept going.
As Professor Kiernan writes, anything that increases central excitability can trigger fasciculations. This includes the fear that they form part of a prodrome to motor neuron disease (MND); a defining characteristic of Fasciculation Anxiety Syndrome in Clinicians (FASICS). Even though my diagnosis of BFS have been “confirmed” by an EMG and a neurologist, I still suffer from occasional episodes of FASICS exacerbations, surfacing like a recurrent nightmare according to its own inner logic. In other words, FASICS undoubtedly shares a quality with health anxiety, namely a jumbled relationship between symptoms and belief. The opening lines of H.P Lovecraft’s “The dreams in the witch house” captures this poetically; “Whether the dreams brought on the fever, or the fever brought on the dreams, Walter Gilman did not know”.
After years of working in hospitals you will have encountered some rare cases where the etiology of a disease have followed a non-standard pathway. These can unconsciously skew your wo...
Show MoreDear Editor,
We read with great interest the recent article by Drs Page & Gaillard describing neuroradiology signs and their variable utility [1].
We recently attempted to bring science to the art of descriptive radiological signs by conducting a randomized controlled trial to assess the utility of these signs for medical student radiology education [2]. We found that ‘Metaphoric Signs’ (linking radiology resemblance to an object or concept which is not actually present in an image) increased descriptive and diagnostic ability as well as students’ lesson enjoyment, when compared to teaching with normal anatomy comparators.
The importance of diagnostic accuracy of commonly used signs was similarly emphasised in our discussion. In addition to being diagnostically accurate, the success of a metaphoric sign also relies on how well it resonates with each individual learner, based on their perception of the real-world similarity alluded to in the radiology image and their prior experiences[3,4]. This is aptly exemplified by Author FG’s stronger association of the pontine appearance in osmotic demyelination with a blockbuster sci-fi trilogy than classical mythology.
An interesting observation in our study was that several students used incorrect wording for the name of the signs yet identified the correct diagnosis. Students who correctly diagnosed agenesis of the corpus callosum from a coronal MRI image containing the ‘Moose head sign’ [5] varia...
Show MoreTo the editor
We greatly enjoyed the excellent recent review on the diagnosis and management of primary lateral sclerosis (PLS). Turner and Talbot emphasize the importance of controlling spasticity as the most troublesome symptom, which is often associated with pain, discomfort and physical disability [1].
Show MoreAs the authors point out, the current standard of care (baclofen, tizanidine, benzodiazepines and botulinum toxin) is frequently complicated by side effects, difficulties in titration and a lack of well controlled clinical studies [2]. We were thus surprised that the authors omitted the option of medicinal cannabis from the discussion of this very important topic.
A study by Riva and colleagues offers clear evidence on the efficacy of the cannabinoid preparation Nabiximol for the control of spasticity in ALS and PLS patients [3], which is further supported by Meyer and colleagues providing compelling real world evidence of this effect [4].
The THC:CBD oromucosal spray (nabioximols, brand name Sativex) became approved in European Union countries in 2010. Although only approved for people with moderate to severe spasticity in multiple sclerosis, who have not responded adequately to other anti-spasticity regimes, THC:CBD is increasingly being used off-label for spasticity in patients with motor neuron diseases. In addition, the patients themselves have self-medicated with recreational cannabis for many years [5].
The multicenter, double-blind,...
We thank Dr Weydt and colleagues for their interest in our review. We are aware of the subjective benefit of cannabinoids reported by some living with multiple sclerosis, and a trial of THC:CDB spray is also approved by the UK’s National Institute for Health & Care Excellence (NICE). The CANALS study mentioned, in which PLS patients were well represented (28% of treatment arm and 20% of placebo arm), was a Phase 2 study powered to consider safety and tolerability. Adverse events were reported in 76% of the treatment group versus 27% in the placebo group. A reduction in the clinician’s Modified Ashworth Spasticity scale score was noted, and in the patient’s numeric rating scale score for pain, but not their scores for spasm or spasticity. In the discussion, the authors note that muscle cramping was not alleviated in a prior randomised trial of THC in ALS (1). We agree with their call for further evaluation, through a Phase 3 study of the benefit of cannabinoids over the licensed therapies for spasticity outlined in our review.
Reference:
1. Weber M, Goldman B, Truniger S. Tetrahydrocannabinol (THC) for cramps in amyotrophic lateral sclerosis: a randomised, double-blind crossover trial. J Neurol Neurosurg Psychiatry. 2010 Oct;81(10):1135-40. doi: 10.1136/jnnp.2009.200642. PMID: 20498181.
It gives more discomfort than pleasure to comment on DaT scanning again but your editorial [1] prompted me to find out that the number of DaTscans carried out in England is increasing yearly, from 4550 in 2012/3 to 8840 in 2018/9. A trip to the dentist might have been wiser, my long-expressed opinion (based on the fundamental principles that let down 18FDopa PET) being that the DaTscan is a waste of time, radiation and money [2]. In brief it is a low resolution, inadequately sensitive, inadequately reproducible test with too many false negatives and little knowledge of confounding influences. The acronym SWEDD has, mercifully, been consigned to the dustbin[3] but we don’t have the neuropathological studies or large and long-term blinded follow-up studies, in patients and healthy individuals, despite the many tests and years since its commercial introduction, that would tell the true false positive and negative rate of the test. We can’t then confidently say how strongly a normal result argues against a clinical diagnosis of PD. Neurology is not the only specialty that uses DaTscan and indication-creep (good for the shareholder, bad for the taxpayer) means that it is also being used to distinguish Lewy Body Dementia from Alzheimer’s Dementia despite limited supportive data (4). It must also be remembered that the test measures biochemistry, not pathology; the statement in the case presentation [5] “a DaTscan was normal, with no evidence of degenerative Parkinsonism” is...
Show MoreWith great interest, we read the review by Markus on personalising the secondary prevention approach to patients with stroke ¹, published in the most recent issue of Practical Neurology. Where we are presented with clinically useful and evidence-based advice for the etiological assessment of patients with acute ischemic stroke (AIS), focusing on lacunar stroke syndromes of a non-lacunar cause, and its appropriate therapeutic management. We consider the article of great importance: a must-read for all physicians who care for patients with AIS since etiological assessment is paramount to dictate the appropriate secondary prevention measures.
The author proposes using the TOAST classification (Trial of Organon 10172 in Acute Stroke Treatment), arguing that classification systems that prime clinical syndromes over pathophysiological mechanisms are less useful. Nevertheless, the author omitted one classification which–partially–resolves the issue: the ASCOD (Atherosclerosis, Small-vessel, Cardiac embolism, Other, Dissection) system ². A comprehensive classification, which allows for more than one aetiology, while giving a degree of a causal relationship to the presence of each category of disease (1 potential, 2 uncertain, 3 unlikely, 0 disease not detected) including incomplete assessment (9 insufficient work-up), while considering some clinical features.
The ASCOD approach permits the identification of patients with diseases that would have been left as indeterm...
Show MoreDear Editors,
Following the publication of the “UK consensus on pregnancy in multiple sclerosis: ABN guidelines” in January 2019, new data has become available and an update is required. Whilst these updates do not change the overall recommendations in the guidelines, they add information, which we feel all neurologists should be aware of in order to provide the highest quality of information to all women with MS considering pregnancy.
(1) Interferon beta preparations in pregnancy
In September 2019, the EMA Committee for Medicinal Products for Human Use (CHMP) recommended a label change for interferon beta-1a, peginterferon beta-1a and interferon beta-1b, i.e. Avonex, Betaferon, Extavia, Plegridy and Rebif, stating that they may be considered during pregnancy if clinically indicated, and can be used during breastfeeding [1]. This decision was based on data from interferon beta registries, national registries and post-marketing experience. However, data from exposure during second and third trimesters remains limited. The duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and it is likely that treatment was interrupted in many women when the pregnancy was detected and/or confirmed.
This supports the recommendation in the “UK consensus on pregnancy in multiple sclerosis: ABN guidelines” that these products are safe to be continued at least until...
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