Recent eLetters

We enjoyed the review by our colleagues Finlayson et al 1 from the United Kingdom, Congenital Myasthenic service, covering all aspects of the congenital myasthenic syndromes. We would, however, suggest that the section on neurophysiology could have been expanded and elaborated more. To state that the neurophysiological findings in congenital myasthenic syndromes are similar to those in autoimmune myasthenia gravis is correct perhaps with respect to repetitive nerve stimulation but when talking about single fibre EMG (SFEMG) it should be emphasised for accuracy that it is stimulated single fibre EMG (StimSFEMG) that should be used in children, certainly under the age of eight years or in the intensive care setting, and not the voluntary SFEMG technique, which requires significant levels of patient cooperation. Furthermore, with most congenital myasthenic syndromes (CMS) having symptoms at birth, which do not always include ptosis, the use of StimSFEMG should be encouraged as it has superior sensitivity in comparison to repetitive nerve stimulation, which makes it the better screening test. The test is well tolerated and is usually performed in the outpatient setting with the child awake. The problem of the specificity of StimSFEMG can be addressed if the technique is used as part of a more wide-ranging neurophysiological examination including nerve conduction studies and EMG examination of limb and bulbar muscles. As an example, demonstration of significant myopathic changes in other muscles will direct the clinician more to the diagnosis of a myopathy with associated secondary neuromuscular transmission defect rather than a primary myasthenic syndrome. We do not hesitate to use Stim SFEMG, which is well tolerated even by the youngest of infants, and consequently we have seen a decrease in both the age at referral for investigation and subsequent diagnosis over the years. This approach has to be encouraged as in several studies it is clear that in many children with CMS, symptoms have been present from birth, which are often non-specific, such as feeding difficulties 2 or stridor 3. Many of us have experienced the consequences of delayed diagnosis, regrettably including sibling death, and we feel that the liberal use of this excellent technique has been a major factor in preventing this by providing an early diagnosis. In an article for a wide readership it is perhaps an omission not to use this opportunity to advertise this technique, available at many Neurophysiological centres (including those of the authors). Hopefully this letter will in part address this oversight.

Reference List

1 Finlayson S, Beeson D, Palace J. Congenital myasthenic syndromes: an update. Pract Neurol 2013;13:80-91.

2 Kinali M, Beeson D, Pitt MC, et al. Congenital Myasthenic Syndromes in childhood: Diagnostic and management challenges 1. J Neuroimmunol 2008 15;201-202:6-12.

3 Jephson CG, Mills NA, Pitt MC, et al. Congenital stridor with feeding difficulty as a presenting symptom of Dok7 congenital myasthenic syndrome. Int J Pediatr Otorhinolaryngol 2010;74:991-994.

Conflict of Interest:

None declared

Turner and Talbot rightly emphasize that in spite of advances in EMG techniques and emergence of novel neuroimaging and CSF biomarkers the diagnosis of motor neuron disease (MND) still remains a clinical one.1 Find upper motor neuron (UMN) and lower motor neuron (LMN) signs in the same limb and MND should be high up in the differential I recall was taught to me in medical school. EMG was to be used in atypical cases where the diagnosis was in doubt. In today's world the pendulum has swung to the other extreme. UMN and LMN signs in the same limb-->could be MND--- >order a 4 limb EMG making certain that tongue and paraspinal musculature is examined-->then make the call-->definite MND Vs probable Vs possible. This over reliance on neuroimaging and neurophysiological data to make the diagnosis is not unique to MND; multiple sclerosis (MS) is another causality. Two discreet attacks separated by time (determined by history) and space (determined by examination findings) and the diagnosis of MS can be made confidently. No MRI brain, visual evoked potentials, somatosensory evoked potentials or oligoclonal bands in CSF are needed. How many of us do that now?

References

1. Turner MR, Talbot K. Motor neurone disease is a clinical diagnosis. Pract Neurol. 2012 Dec; 12(6):396-7.

Conflict of Interest:

None declared

I enjoyed Fuller's description of 'neurophilia' - we can finally label this condition afflicting neurologists, and recognise that is widespread within medicine and the general population.(1) Neurophilia is probably infectious (i.e. environmental); my personal experience and informal discussions with neurology colleagues revealed that many chose neurology as a career following positive experiences during their Senior House Officer jobs. This emphasizes the suggestion that neurophobia can be dispelled and neurophilia encouraged through effective, inspirational teaching, accessible textbooks and journals.

However, I would also like to highlight a potential genetic contribution. In the UK, I am aware of at least 6 neurological families - those families where more than one first degree relatives are neurologists. - many more than would be expected by chance. This does suggest that neurophilia may have genetic as well as environmental elements.

Reference 1. Fuller GN. Neurophilia: a fascination for neurology--a new syndrome. Practical Neurology. 2012;12(5):276-8.

Conflict of Interest:

Dr Wong is a committed neurophile

The term generalized in EEG is certainly ambiguous and can be a cause of confusion, especially to a reader who is not formally trained in neurophysiology. As a neurology resident in training, the importance of personally reviewing the patient's CT or MRI scan was impressed upon me time and time again. Do not just take the radiologist's report at face value, look at the pictures yourself since you after seeing the patient know what to look for better than the radiologist, was the pearl of wisdom imparted to me by a seasoned neurologist. While a similar argument can be made for reviewing the EEG too, interpretation of EEG is a skill which is not formally taught during residency training. So is there a way out? The answer is yes and it requires reading the body of the EEG report and not just the final impression. Is the background frequency normal or slow? What is the morphology and distribution of the spike wave discharges: slow spike and wave (secondary generalized seizure disorder) versus 4-6 Hz polyspike and wave discharges (primary generalized seizure disorder). EEG reporting truly is like trying to translate a picture into words. One though needs to see the entire picture and not just the impression at the end.

Conflict of Interest:

None declared

In the Saifee TA et al article (1) regarding the treatment of "Tardive movment disorders" (TD), the authors recommend the use of amantadine as second or third line among other possible drugs ("each with fairly limited evidence for effectiveness" in author?s words).

In 1971, the late Dr. Espejel and I informed for the first time the benefits of amantadine in drug-induced dyskinesias (2); consequently, I have followed with interest the derived articles. Failures and successes are reported with the use of this agent. Here, I am interested to comment the possible cause about the failures in TD treatments with amantadine, to bring together data that may generate a "personalized" prescription yielding an increased number of benefited patients.

Drugs-induced dyskinesias are a heterogeneous number of disorders with different pathophysiological mechanisms in their generation: presynaptic excess of dopamine formation, postynaptic supersensitive dopaminergic receptors, or glutamergic overactivity mediated by the N- methyl-D-aspartic acid (NMDA) receptor, all them grouped in an apparently homogenous syndrome.

So, it is important to know if the patient we are treating are within the glutamergic overactivity mediated by the NMDA receptor subset, since only in these patients will obtain good results when treated with drugs like amantadine or other well-tolerated NMDA receptor antagonist (3). However, how do we can investigate this phenotypic feature? Brain MRI spectroscopy can reveal the NMDA receptors excess but its high cost may limit its routine use. However, if we bear in mind that patients with low NMDA activity are clinically hypoactive and anhedonic and have exaggerated extrapiramidal sensitivity (4), they will be prone to suffer TD amantadine -resistant. Therefore, give amantadine in affected TD patients with hyperactivity preferentially (or at least with normal motor activity) to obtain better responses.

References:

1. Saifee TA, Edwards MJ. Tardive movement disorders: a practical approach. Pract Neurol 2011;11:341-348

2. Vale S, Espejel MA. Amantadine for dyskinesia tarda. N Engl J Med. 1971;284:673.

3. Del Dotto P, Pavese N, Gambaccini G, Bernardini S, Metman LV, Chase TN, Bonuccelli U. Intravenous amantadine improves levadopa-induced dyskinesias: an acute double-blind placebo-controlled study. Mov Disord. 2001;16:515-20.

4. Telfer S, Shivashankar S, Krishnadas R, McCreadie RG, Kirkpatrick B. Tardive dyskinesia and deficit schizophrenia. Acta Psychiatr Scand. 2011;124:357-62.

Conflict of Interest:

None declared