In 2009 GE Healthcare revealed that 219,000 people had undergone the
Datscan test [1]; by now it must be many more. The review article [2] by
one employee of the company and two GE Healthcare sponsored clinicians
considers the utility of the test. They begin by disparaging experienced
clinical assessment. It is unarguable that expertise at a specialised
centre doesn't extend to general practice (they cite a study from...
In 2009 GE Healthcare revealed that 219,000 people had undergone the
Datscan test [1]; by now it must be many more. The review article [2] by
one employee of the company and two GE Healthcare sponsored clinicians
considers the utility of the test. They begin by disparaging experienced
clinical assessment. It is unarguable that expertise at a specialised
centre doesn't extend to general practice (they cite a study from North
Wales in 1999 that found that 47% of patients diagnosed did not fulfil
Parkinson's Disease Brain Bank Criteria (PDBBC)} but this is a comment on
education and service delivery, not the accuracy of experienced clinical
diagnosis. They cite a study in which a full clinical assessment, with
history and examination, was replaced by a videotape of patients with
tremor. They go on to damn clinical assessment with faint praise, and I
quote, "in practice clinical diagnosis is sufficient for many patients
with advanced and typical manifestations of PD", thus ignoring the many
years of clinical experience that tell us that in practice clinical
diagnosis at symptom onset is usually correct [3] and when it isn't, then
time or a second opinion often help. Patients may be happy to wait, and
to allow the clinical picture to become clearer, before they decide to
take medication.
The authors then consider why between 4 and 15% of PD patients
fulfilling PDBBC have a normal Datscan. I repeatedly explained to the
manufacturers (then Amersham International) and many of their sponsored
clinicians many years ago that, based on experience with 18Fdopa PET
scanning, I was concerned that the technique showed insufficient
separation between the range of values in the healthy population and that
in the de-novo PD population; one could however establish the rate of
false negatives in a de-novo PD population by comparing mean and standard
deviation in this group with mean and standard deviation of an age-matched
healthy population, the larger the sample sizes the better. They didn't
listen and that study has never been carried out. In fairness to them,
regulations wisely prevent the exposure of too many healthy people to
radio-pharmaceuticals. My estimate in 2005, based on the limited data
then available, was that the majority of the so-called SWEDD's would be
false negatives [4]. The quoted long-term follow-up of SWEDD's in the
ELLDOPA study (that has appeared in abstract only) was for a maximum of
six years. The heterogeneity of progression in Parkinsonism (in Hoehn
and Yahr's study [5] the average duration of life after diagnosis varied
between one and thirty three years) means that short term follow-up has
little value. Until every SWEDD has been followed up for many years,
ideally to post-mortem, then the authors shouldn't imply that SWEDD's are
likely to represent misdiagnoses. But the de-novo population is one in
which around 90% will, by clinical assessment, have PD. In a population
in which only 50% have parkinsonism as, for example, when separating PD
from ET then, using the same data sources as above, Bayes theorem tells
that the chance of an erroneous diagnosis may be as high as 50%.
There are other issues to consider. The quoted national Datscan
audit showed that one in twenty five Datscans were misreported in the 50%
of centres that took part in the audit; we don't know the rate of
misreporting in the other centres. A further problem for what is
essentially an in-vivo biochemical measurement is that few human studies
have been carried out with commonly used medications (for example anti-
psychotics, anti-hypertensives or anti-depressants) that could affect scan
results. With regard to quantitation the authors state that "the routine
clinical use of quantitation...... cannot be recommended for clinical
practice without a visual read". The picture we see is a colour scale
interpretation of the numbers generated by the scan's detectors and
computer; if quantitation can't be recommended, how can the authors
recommend assessing the resulting images by eye?
Eventually, after undermining clinical assessment and hinting loudly
that the visually normal scans in patients presenting as clinical PD are
explained by clinicians' diagnostic errors, the authors acknowledge that
the true accuracy of the test is unknown.
For a test to have clinical utility in helping us confidently tell a
patient whether they have PD or not, we need to know the false negative
and false positive rate in de-novo patients, the rate of error in image
reporting in all centres, and the effect of all medications that a patient
might be taking. That it has been used so extensively without this
information represents a triumph of persuasive marketing over clinicians'
common sense. That so many people have been exposed to radiation (one
quoted author [2] has put the risk of cancer at 1 in 5000) for a test with
such limitations is a worry. Instead of the 100% reliable, very safe and
inexpensive test that we and our patients might want, we have false
negatives (number unknown), misreading of scan images (4% in 50% of
centres), possible confounding effects of medication (unknown), expense
(around 800 UK pounds or 1500 US dollars per scan) and a significant risk
of cancer.
When given these facts and figures, patients will surely prefer to
trust a clinician who is aware of their own limitations than a scan that
has more limitations than is publicly acknowledged.
References:
1.
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PeripheralandCentralNervousSystemDrugsAdvisoryCommittee/UCM186404.pdf
(accessed February 2014)
2. Bajaj N, Hauser RA and Grachev ID. Clinical utility of dopamine
transporter single photon emission CT (DaT-SPECT) with (123I) ioflupane in
diagnosis of parkinsonian syndromes. J Neurol Neurosurg Psychiatry 2013;
84:1288-1295
3. De la Fuente-Feernandez R. Role of DaTSCAN and clinical diagnosis in
Parkinson's disease. Neurology 2012; 78:696-701
4. Morrish PK. Controversies in Neuroimaging. 2008 Chapter 28 in
Parkinson's disease; Diagnosis and Clinical Management. Demos Publishing
(New York). Eds Factor and Weiner
5. Hoehn MM, Yahr MD. Parkinsonism: onset, progression, and mortality.
Neurology 1967;17:427-42.
Conflict of Interest:
In 2001 I was interviewed for a job with what was then Amersham international. I used the interview to tell the company of my concerns about the test (based on my experience with 18Fdopa PET scanning). Not surprisingly I decided that I didn't want the job and they decided that they didn't want to employ me.
We thank Hirata et al. for their thoughtful letter in response to
our recent Case of the Month.[1] Their case is another example of covert
benzodiazepine administration , perhaps even Munchausen syndrome by proxy,
a condition that we suspect is much under-recognised in an adult setting.
Elsewhere, we have reviewed the concept of endozepine stupor [2] and
agreed with the Bologna group's vi...
We thank Hirata et al. for their thoughtful letter in response to
our recent Case of the Month.[1] Their case is another example of covert
benzodiazepine administration , perhaps even Munchausen syndrome by proxy,
a condition that we suspect is much under-recognised in an adult setting.
Elsewhere, we have reviewed the concept of endozepine stupor [2] and
agreed with the Bologna group's view [3] that the existence of this entity
is unproven. Indeed, we suspect that previous cases were all probably due
to covert benzodiazepine administration. Further putative examples of
endozepine stupor will require exhaustive and sophisticated toxicological
analysis for benzodiazepines before they can be accepted as evidence for
the existence of this syndrome.
References
(1)Granot R, Berkovic SF, Patterson S, Hopwood M, Mackenzie R.
Idiopathic recurrent stupor: a warning. J Neurosurg Psychiatry 2004;75:368
-9.
(2) Granot R, Berkovic SF, Patterson S, Hopwood M, Drummer O,
Mackenzie R. Endozepine stupor: disease or deception? Sleep 2004; in
press.
(3) Lugaresi E, Montagna P, Tinuper P, Plazzi G, Gallassi R.
Suspected covert lorazepam administration misdiagnosed as recurrent
endozepine stupor. Brain 1998; 121: 2201.
With great interest we read the article by Böckle et al (1), who
report a patient with muscle atrophy preceding bilateral linear morphea.
We would like to confirm the importance of recognizing linear scleroderma
as an unusual cause of focal muscle atrophy. Recently we described a
similar case (2) and would like to comment on various aspects of Böckle’s
report.
With great interest we read the article by Böckle et al (1), who
report a patient with muscle atrophy preceding bilateral linear morphea.
We would like to confirm the importance of recognizing linear scleroderma
as an unusual cause of focal muscle atrophy. Recently we described a
similar case (2) and would like to comment on various aspects of Böckle’s
report.
Their case is unusual since the myopathy preceded the skin changes,
and because the muscle atrophy was unrelated to the site of the skin
involvement. Our patient suffered from progressive muscle atrophy while
skin changes had been in remission for years. Hence, muscle involvement in
linear scleroderma may occur independently of the sclerotic skin changes,
both in time and in location. The authors describe that EMG at onset
revealed neuropathic changes in the triceps brachii muscle. We performed
subsequent EMGs in several muscles of our patients affected limb, but
found predominantly myopathic motor units, with short-duration and low-
amplitude units and spontaneous activity (fibrillations, positive spikes,
and complex repetitive discharges). In fact, the amount of spontaneous
activity matched the clinical course and therapy effect in our patient.
The muscle biopsy in Böckle’s report displayed a terminal stage of
muscular damage. In our patient, the first biopsy of the brachioradialis
muscle showed no abnormalities while a second biopsy of the biceps brachii
muscle only revealed end-stage fibrosis. With use of muscle MRI and muscle
ultrasound, the deltoid muscle was selected as the correct site of biopsy,
and here a focal myositis was demonstrated that was decisive for the
diagnosis of linear scleroderma with deep morphea. Not only skin sclerosis
but also muscle inflammation occurs in linear streaks, and sampling error
can easily occur. Therefore, the site of muscle biopsy should be selected
carefully, preferably with the help of muscle imaging.
The patient in Böckle’s report was referred to the outpatients
department for autoimmune disease only when blood analysis revealed a high
titer of antinuclear antibodies, six years after onset of the muscle
weakness of his left triceps. There, he presented with an indurated area
of the back of his right hand and forearm, and skin biopsy was indicative
for linear scleroderma. This course suggests that neurologists may not be
trained to be alert to the dermal changes that were the clue to this
diagnosis. Furthermore, linear scleroderma often presents without high
titer of antinuclear antibodies
Böckle et al report good effect of treatment with balneophototherapy
and methylprednisolon. As our patient did not improve with oral prednisone
and low-dose methotrexate, we had to resort to higher dose subcutaneous
methotrexate in combination with UVA1 phototherapy. This was well
tolerated and resulted in considerable improvement of skin sclerosis and
reduction of contractures. Muscle strength and mass has not improved yet;
this may indicate that the deep morphea has already resulted in end-stage
myopathy.
Linear scleroderma is a striking cause of focal myositis causing
atrophy and weakness, Neurologists should consider this diagnosis in
patients with segmental muscle weakness and atrophy, also when skin
lesions are minimal or not progressive. Serious disability may be
prevented with appropriate immunosuppressive treatment.
References
(1) Böckle BC, Willeit J, Freund M, Sepp NT. Unexplained muscle atrophy as the unique preceding symptom of bilateral linear morphea.
J Neurol Neurosurg
Psychiatry 2009;80:310-1.
(2) Voermans NC, Pillen S, de Jong EM, Creemers MC, Lammens M, van Alfen N Morphea profunda presenting as a
neuromuscular mimic.
J Clin Neuromuscul Dis 2008;9:407-14.
Recently Linn et al. compared visual with spectrophotometric
assessment of xanthochromic cerebrospinal fluid (CSF) and concluded that a
sample perceived as colourless is incompatible with the diagnosis of
recent subarachnoid haemorrhage (SAH).[1] Six CSF samples spiked with
bilirubin and one normal CSF sample were assessed by 102 subjects
visually. Spectrophotometry between 450–460 nm established extinc...
Recently Linn et al. compared visual with spectrophotometric
assessment of xanthochromic cerebrospinal fluid (CSF) and concluded that a
sample perceived as colourless is incompatible with the diagnosis of
recent subarachnoid haemorrhage (SAH).[1] Six CSF samples spiked with
bilirubin and one normal CSF sample were assessed by 102 subjects
visually. Spectrophotometry between 450–460 nm established extinctions
from 0.01 to 0.09 in the six spiked samples.
The observations made by Linn et al. are valuable, albeit our
interpretation of their results differs from their own. We think that the
study confirms that visual assessment of the CSF for low concentrations of
bilirubin is inferior to spectrophotometry. To illustrate this point we
compare in Table our own results contrasting visual with
spectrophotometric detection of low concentrations of bilirubin with those
of Linn et al.[1,2] For this post–hoc analysis, we have only included
the observed frequencies of their samples seen as “yellow” or as
“colourless”. Samples for which no decision could be made because the
visual inspection was “doubtful” are not included. Clearly, both sets of
data demonstrate that human colour vision is less sensitive than
spectrophotometry for detecting small amounts of bilirubin from the CSF.
It would be interesting to analyse the original absorption spectra of the
Linn et al.[1] to determine whether their visual threshold (extinction of
0.06) corresponds to ours (excitation purity or saturation of about 2.4%).[2]
We would like to pose three additional questions: (1) Why was an
arbitrary cutoff of 0.05 chosen as opposed to 0.023 which was the
criterion published by the same group previously[3]? (2) Why was a
spectral bandwidth (450–460 nm) selected for measuring an extinction as
opposed to the recommended absorbance at 476 nm[4]? (3) Given that the
major “real life” problem for visual assessment of CSF from a recent SAH
is likely to be contamination with blood (of red colour)[5], why was
visual assessment restricted to a sensitivity problem (i.e., detection of
low concentrations of bilirubin in an otherwise colourless sample)? If
one extrapolates from previous data[3] such an analysis is more
appropriate for CSF samples taken quite some time after a SAH, rather
than, as the authors intended, recently following a SAH.
References
[1] F.H. Linn, H.A. Voorbij, G.J. Rinkel, A. Algra, and J. van Gijn.
Visual inspection versus spectrophotometry in detecting bilirubin in
cerebrospinal fluid. J Neurol Neurosurg Psychiatry, 76:1452–1404, 2005.
[2] A. Petzold, G. Keir, and T.L. Sharpe. Why human color vision
cannot reliably detect cerebrospinal fluid xanthochromia. Stroke,
36:1295–1207, 2005.
[3] M. Vermeulen, D. Hasan, B.G. Blijenberg, A. Hijdra, and J. van
Gijn. Xanthochromia after subarachnoid haemorrhage needs no revisitation.
J Neurol Neurosurg Psychiatry, 52:826–808, 1989.
[4] UK NEQAS. National guidelines for analysis of cerebrospinal fluid
for bilirubin in suspected subarachnoid haemorrhage. Ann Clin Biochem,
40:481–408, 2003.
[5] A Petzold, G Keir, and LT Sharpe. Spectrophotometry for
xanthochromia. N Engl J Med, 351:1695–1696, 2004.
Axel Petzold MD PhD
Department of Neuroimmunology, ION
The Tavistock Intensive Care Unit, NHNN
Queen Square
London WC1N 3BG, United Kingdom
Tel.: +44 207837 3611 x4204
Fax: +44 207837 8553
E-mail: a.petzold@ion.ucl.ac.uk
Lindsay T. Sharpe PhD
Institute of Ophthalmology
11-43 Bath Street
London EC1V 9EL, United Kingdom
Table aThe statistics are based on the numbers from Table 1 in reference [1]: for an extinction of 0.09 none of
the clinicians or medical students saw the sample as colourless (n=0), 50 clinicians and 49 students saw the
sample as yellow (n=99), and 1 clinician and 2 students were undecided and therefore left out of this analysis.
In contrast spectrophotometry clearly revealed the presence of bilirubin and all clinicians and students would
have interpreted the spectrophotometric trace in the same way (n=102). The numbers for the other extinctions
were analysed analogously.
We have read with great interest the work of Dhollander et al. [1]
and express our congratulation for their wonderful work, but we would like
to add some considerations.
The authors describe two patients presenting clinically transient
neurological deficit and radiologically with a focal cortical subarachnoid
haemorrhage in the brain CT and multifocal cortical siderosis in brain MR.
They compare their patients with the clas...
We have read with great interest the work of Dhollander et al. [1]
and express our congratulation for their wonderful work, but we would like
to add some considerations.
The authors describe two patients presenting clinically transient
neurological deficit and radiologically with a focal cortical subarachnoid
haemorrhage in the brain CT and multifocal cortical siderosis in brain MR.
They compare their patients with the classical diagnosis of superficial
siderosis but remark the differences with that diagnosis and propose the
term of cortical superficial siderosis.
We think from a radiological point of view it is better to consider these
patients as having suffered a focal cortical convexity subarachnoid
haemorrhage (cSAH), a term previously proposed in the literature [2;3]. In
this way there are some works showing a wide differential diagnosis
between the different aetiologies of cSHA including vasculitic, toxic,
pharmacological, vascular and amyloid angiopathy related causes. In an
interesting manner some reviews have shown how, in the older group of age,
all the cases were associated with amyloid angiopathy [3].
And, secondly, when cSAH appears in the elderly, the clinical
manifestations of transient neurological deficit are repeatedly described
and the hypotheses about its physiopathology have been related to cortical
spreading depression [4;5].
For these reasons we think this clinico-radiological picture of a
cSAH in the brain CT of an elderly patient presenting with neurological
transient deficitary manifestations is emerging as one of the
manifestations of cerebral amiloyd angiopathy, aside from lobar
haemathoma.
It is remarkable the elegant demonstration of Dhollander et al. [1]
of beta-amyloid deposition, in their patients, in the regions of the brain
usually involved in Alzheimer disease and, especially, in the areas
previously affected of a focal cortical subarachnoid bleeding. In our
knowledge this has not previously been reported as a demonstration of
amyloid pathology in cSAH.
1. Dhollander I, Nelissen N, Van Laere K, Peeters D, Demaerel P, Van
Paesschen W, Thijs V, Vandenberghe R. In vivo amyloid imaging in cortical
superficial siderosis. J Neurol Neurosurg Psychiatry 2011;82:469-71.
2. Spitzer C, Mull M, Rohde V, Kosinski CM. Non-traumatic cortical
subarachnoid haemorrhage: diagnostic work-up and aetiological background.
Neuroradiology 2005;47:525-31.
3. Kumar S, Goddeau RP, Jr., Selim MH, Thomas A, Schlaug G,
Alhazzani A, Searls DE, Caplan LR. Atraumatic convexal subarachnoid
hemorrhage: clinical presentation, imaging patterns, and etiologies.
Neurology 2010;74:893-9.
4. Izenberg A, Aviv RI, Demaerschalk BM, Dodick DW, Hopyan J, Black
SE, Gladstone DJ. Crescendo transient Aura attacks: a transient ischemic
attack mimic caused by focal subarachnoid hemorrhage. Stroke 2009;40:3725-
9.
5. Brunot S, Osseby GV, Rouaud O, Kazemi A, Ricolfi F, Couvreur G,
Catteau A, Hervieu M, Moreau T, Giroud M, Bejot Y. Transient Ischaemic
Attack Mimics Revealing Focal Subarachnoid Haemorrhage. Cerebrovasc Dis
2010;30:597-601.
I have read your article(1) with interest ,which is also a very good study .However, in this connection I would like to mention that ,in your study the mean time of recording the EEG is almost double in sleep deprivation EEG than that of routine EEG. Whether this long duration of recording in sleep deprived cases has given much more abnormal EEG than that of others and whether sleep deprived EEG should b...
I have read your article(1) with interest ,which is also a very good study .However, in this connection I would like to mention that ,in your study the mean time of recording the EEG is almost double in sleep deprivation EEG than that of routine EEG. Whether this long duration of recording in sleep deprived cases has given much more abnormal EEG than that of others and whether sleep deprived EEG should be taken for longer duration in all cases, to get a higher yield is the question. Also whether sleep deprived EEG should be a routine procedure in young adults with newly diagnosed epilepsy?
Although many studies have shown that the yield of abnormal EEG is profound in patients suspected of having epilepsy after a sleep deprived EEG, but it is to be noted that all night sleep deprivation prior to EEG recording causes much inconvenience to the patient, as well as to the family members especially in pediatric cases. Degen R et al (2) in a study of EEG of 190 patients reported the activation rate of epileptic activity in 52.6% (without sleep deprivation) and 53.2%(with sleep deprivation) and
also noted no real differences between the two methods in classifying the epileptic discharges. Kubicki S et al (3) reported electroencephalographic activity indicative of seizure disorder in 53.6%in patients suspected to have epilepsy, when a short term sleep EEG recorded following a partial sleep deprivation during the previous night. Evangeline et al(4) have found melatonin induced sleep EEG was as informative as sleep deprived EEG in pediatric groups. Melatonin also do not alter the microstructure of
sleep. Milstein et al (5) reported melatonin induced sleep recording to be safe and reliable in adults.
Considering all these factors, I think it is better to carry out a study in adult patients to prove that partial sleep deprivation during previous night followed by a melatonin induced sleep recording can yield the same information as that of a total sleep deprivation recording. It is then that a protocol for EEG recording with total sleep deprivation in newly diagnosed epileptic patients is to be considered.
REFERENCES
1 JP Leach, LJ Stephen, C Salveta, M J Brodie--Which
electroencephalography(EEG)for Epilepsy? The relative usefulness of different EEG protocols in patients with possible epilepsy.J Neurol Neurosurg Psychiatry, 2006, 77, 1040-1042.
2 Degen R, DegenH E, Reker M---Sleep EEG or without sleep deprivation? Does sleep deprivation activate more epileptic activity in patients suffering from different types of epilepsy? Eur Neurol.1987, 26(1):51-9 Abstract PubMed.
3 Kubicki S, Scheuler W,Wittenbecher H---Short term sleep EEG recordings after partial sleep deprivation as a phenomena: an evaluation of 719 EEG recordings.Epilepsy Res Suppl. 1991,2:217-30.Abstract PubMed
4 Evangeline Wassmer,Paul F B Carter, Gina Welsh, Stefano Seri, William P Whitehouse--Melatonin is useful for recording sleep EEG a prospective audit of outcome,--Developmental Medicine&Child Neurology,2001,43,735-738
With great interest we have read the research paper by Kingwell et
al. on cancer risk with interferon-beta (IFNb) treatment in MS. The
authors cautiously conclude that a possible association between IFNb usage
and the occurrence of breast cancer should be investigated further.
Although the authors interpret their overall finding as reassuring that
overall cancer risk does not seem to be increased in IFNb users, they
disc...
With great interest we have read the research paper by Kingwell et
al. on cancer risk with interferon-beta (IFNb) treatment in MS. The
authors cautiously conclude that a possible association between IFNb usage
and the occurrence of breast cancer should be investigated further.
Although the authors interpret their overall finding as reassuring that
overall cancer risk does not seem to be increased in IFNb users, they
discuss the possibility that IFNb might indeed enhance tumour growth, as
suggested by others.1
They did not address, however, a possible role of neutralizing
antibodies (NAb) to IFNb. It is well established that NAb developed during
treatment with recombinant IFNb can persist for years, even after
cessation of IFNb treatment.2,3 NAb are able to abolish the efficacy of
IFNb treatment and have been shown to block endogenous IFNb as well.3,4 It
is not implausible that persisting Nab may induce long term lack of IFNb
bioactivity and thereby may increase the vulnerability to certain forms of
cancer; given the anti-viral properties of IFNb probably especially those
forms that are virus-induced.
Therefore, the authors might consider to address this important issue
by correlating cancer risk specifically to the occurrence of persisting
anti-IFNb NAb in their large Canadian cohort of MS patients.
Laura F van der Voort,
Joep Killestein
1 Gibbs E, Tremlett H, Ball N, et al. Malignant melanoma in a
multiple sclerosis
patient with persistent neutralizing antibodies to interferon-beta. Eur J
Neurol
2008;15:e4.
2 Petersen B, Bendtzen K, Koch-Henriksen N, Ravnborg M, Ross C,
Sorensen PS; Danish Multiple Sclerosis Group. Persistence of neutralizing
antibodies after discontinuation of IFNbeta therapy in patients with
relapsing-remitting multiple sclerosis. Mult Scler. 2006 Jun;12(3):247-52.
3 van der Voort LF, Gilli F, Bertolotto A, Knol DL, Uitdehaag BM,
Polman CH, Killestein J. Clinical effect of neutralizing antibodies to
interferon-beta that persist long after cessation of therapy for multiple
sclerosis. Arch Neurol 2010 April;67(4):402-7.
4 Sominanda A, Lundkvist M, Fogdell-Hahn A, Hemmer B, Hartung HP,
Hillert J, Menge T, Kieseier BC. Inhibition of endogenous interferon beta
by neutralizing antibodies against recombinant interferon beta. Arch
Neurol. 2010 Sep;67(9):1095-101.
Conflict of Interest:
J. Killestein: has received consulting fees from Merck-Serono, Teva, Biogen Idec, Genzyme and Novartis. VU Medical Center has received financial support for research activities from Bayer Schering Pharma, Biogen-Idec, GlaxoSmithKline, Merck Serono, Novartis, and Teva.
I read with interest the article by Yogarajah et al 1. Working in a
comprehensive epilepsy center of a tertiary referral hospital in the
United States, I found the cost benefit analysis of long term monitoring
(LTM) either by video telemetry (VT) or inpatient ambulatory
electroencephalography (aEEG) useful information indeed. I agree with the
authors that one of the greatest utility of LTM lies in...
I read with interest the article by Yogarajah et al 1. Working in a
comprehensive epilepsy center of a tertiary referral hospital in the
United States, I found the cost benefit analysis of long term monitoring
(LTM) either by video telemetry (VT) or inpatient ambulatory
electroencephalography (aEEG) useful information indeed. I agree with the
authors that one of the greatest utility of LTM lies in its ability to
distinguish epileptic disorders from non-epileptic events (NEE).
Distinguishing between these two groups of patients early on helps to cut
down costs and improves quality of life issues.
In my experience, I have also found LTM especially beneficial to rule
out non-convulsive seizures in patients admitted to the intensive care
unit with depressed levels of sensorium and in clarifying the diagnosis in
patients with infrequent paroxysmal events. In our center we do not do
inpatient aEEG studies and the authors demonstration that inpatient aEEG
is as effective as VT in distinguishing between NEE, focal and generalized
epilepsy is very important as it can significantly help reduce cost of
care.
The above information though is not being taught to residents and
others in training who frequently order LTM in patients in whom the
diagnosis may be clarified by a routine 30 minutes EEG study. Cutting
costs is a priority in today’s managed care systems and the most effective
way would be by educating the neurology community in better identifying
those patients who shall truly benefit from LTM.
References
1. Yogarajah M, Powell HW, Heaney D, Smith SJ, Duncan JS, Sisodiya
SM. Long term monitoring in refractory epilepsy: the Gowers Unit
experience.
J Neurol Neurosurg Psychiatry. 2009; 80(3):305-10.
Baurmann was the first to explain the physilogical conditions of the
central retinal venous pulse (collapse). We reassessed the experimental
setting by a new technical model. We could confirm the results of
Baurmann. The experiment as well as clinical investigations show that
venous collapse can be used to exactly measure the intravasal pressure in
the outflow vein (therefore we created the term - venou...
Baurmann was the first to explain the physilogical conditions of the
central retinal venous pulse (collapse). We reassessed the experimental
setting by a new technical model. We could confirm the results of
Baurmann. The experiment as well as clinical investigations show that
venous collapse can be used to exactly measure the intravasal pressure in
the outflow vein (therefore we created the term - venous outflow
pressure). As the outflow vein (extraocular part of the central retinal
vein) passes for a short strech through the optic nerve - which is
enclosed in a sleeve of cerebrospinal fluid, the intraocular pressure
cannot be lower than the pressure within the optic nerve. This is why we
can assess the intracranial pressure by the venous outflow pressure.
But there is a peculiarity in detecting the venous pulse: Beside the
wellknown venous pulse we also have a non pulsating venous "collapse".
This peculiarity may have prevented a broadly accepted explanation for the
central retinal venous pulse / collapse.
References
Rolf Meyer-Schwickerath et al. Central retinal venous outflow pressure.
Graefe's Arch Clin Exp Ophthalmol (1995)233: 783-788
We write in relation to the editorial commentary from Khan et Tselis
(1) who rightly suggest caution to consider chronic cerebrospinal venous
insufficiency (CCSVI) as a pathological entity and cast serious doubt on
its relevance to multiple sclerosis (MS); they forecast properly designed
studies to investigate the relevance of CCSVI to MS, in order to carry out
interventional procedures.
The absence of extracranial venous...
We write in relation to the editorial commentary from Khan et Tselis
(1) who rightly suggest caution to consider chronic cerebrospinal venous
insufficiency (CCSVI) as a pathological entity and cast serious doubt on
its relevance to multiple sclerosis (MS); they forecast properly designed
studies to investigate the relevance of CCSVI to MS, in order to carry out
interventional procedures.
The absence of extracranial venous stenosis at the earliest stage of MS
makes it an unlikely cause of the disease (2). The idea of venous
congestion as a possible contributor to the pathogenesis of MS has been
discussed for the past 40 years, but remained widely unappreciated by the
scientific community.
In contrast with other authors, Zamboni et al (3) defined CCSVI as a
vascular condition associated with MS; it is characterized by multiple
intraluminal stenosing malformations of the principal pathways of
extracranial venous drainage, particularly in the internal jugular veins
(IJVs) and the azygous vein (AZY), that restrict the normal outflow of
blood from the brain.
In the study of Zamboni et al there was significant extracranial venous
stenosis localised at the principal level of the cerebrospinal venous
segments as detected by selective venography and anomalies of venous
outflow at color Doppler high resolution examination. The pathological
consequences of CCSVI have been hypothesised to emanate from chronic
venous reflux and hypertension leading to increased iron deposition in the
brain and subsequent MS pathology, including inflammation and
neurodegeneration. Other recent reports found no differences in
cerebrospinal venous drainage using transcranial and extracranial Doppler
imaging (4-5).
The discrepancies in the results may be explained with the absence of
standardized internationally accepted criteria for normal Doppler venous
flow parameters (2).
We performed complete post-mortem examination of two patients with MS,
died for different causes. One patient, a 74 year-old-woman, was
hospitalized for acute respiratory illness and died because of bacterial
pneumonia; the other one, a 35 year-old-woman, died for otogenic bacterial
meningitis complicated with internal jugular thrombosis as demonstrated on
MR venography.
Postmortem examination demonstrated in both patients a marked stenosis of
left internal jugular vein at the apex of the angle formed by the two
heads of the sternocleidomastoid muscle where the IJV overlie the carotid
artery with ectasia and congestion of the intracranial veins. Venous flow
slowing, caused by the stenosis, had predisposed to IJV thrombosis,
histologically demonstrated in the second case.
Severe inflammatory disease may be a risk factor for deep venous
thrombosis but also chronic cerebrospinal venous insufficiency.
We demonstrate, for the first time as far as we are aware, the presence
of anatomical alteration in the veins of the neck with impaired venous
drainage from the central nervous system in two patients with multiple
sclerosis who died from other causes. We do not know the exact
implications in MS pathology and certainly there is no doubt that this
area warrants a great deal more study. Clinical trials for evaluating new
therapeutic agents and other clinical experimental protocols may be
required.
References
1. Khan O, Tselis A.
Chronic cerebrospinal venous insufficiency and multiple sclerosis: science
or science
fiction?
J Neurol Neurosurg Psychiatry 2011;82:355.
2. Yamout B, Herlopian A, Issa Z
Extracranial venous stenosis is an unlikely cause of multiple sclerosis
Mult Scler 2010 16: 1341-9
3. Zamboni P, Galeotti R, Menegatti E, et al
Chronic cerebrospinal venous insuffiency in patients with multiple
sclerosis.
J Neurol Neurosurg Psychiatry 2009;80:392-9.
4. Doepp F, Paul F, Valdueza JM, et al
No cerebrocervical venous congestion in patients with multiple sclerosis.
Ann Neurol 2010, 68:173-183.
5. Sundstrom P, Wahlin A, Ambarki K, et al
Venous and cerebrospinal fluid flow in multiple sclerosis: a case-control
study.
Ann Neurol 2010, 68:255-259.
In 2009 GE Healthcare revealed that 219,000 people had undergone the Datscan test [1]; by now it must be many more. The review article [2] by one employee of the company and two GE Healthcare sponsored clinicians considers the utility of the test. They begin by disparaging experienced clinical assessment. It is unarguable that expertise at a specialised centre doesn't extend to general practice (they cite a study from...
Dear Editor
We thank Hirata et al. for their thoughtful letter in response to our recent Case of the Month.[1] Their case is another example of covert benzodiazepine administration , perhaps even Munchausen syndrome by proxy, a condition that we suspect is much under-recognised in an adult setting.
Elsewhere, we have reviewed the concept of endozepine stupor [2] and agreed with the Bologna group's vi...
Dear Editor,
With great interest we read the article by Böckle et al (1), who report a patient with muscle atrophy preceding bilateral linear morphea. We would like to confirm the importance of recognizing linear scleroderma as an unusual cause of focal muscle atrophy. Recently we described a similar case (2) and would like to comment on various aspects of Böckle’s report.
Their case is unusual since t...
Dear Editor,
Recently Linn et al. compared visual with spectrophotometric assessment of xanthochromic cerebrospinal fluid (CSF) and concluded that a sample perceived as colourless is incompatible with the diagnosis of recent subarachnoid haemorrhage (SAH).[1] Six CSF samples spiked with bilirubin and one normal CSF sample were assessed by 102 subjects visually. Spectrophotometry between 450–460 nm established extinc...
We have read with great interest the work of Dhollander et al. [1] and express our congratulation for their wonderful work, but we would like to add some considerations. The authors describe two patients presenting clinically transient neurological deficit and radiologically with a focal cortical subarachnoid haemorrhage in the brain CT and multifocal cortical siderosis in brain MR. They compare their patients with the clas...
Dear Editor,
I have read your article(1) with interest ,which is also a very good study .However, in this connection I would like to mention that ,in your study the mean time of recording the EEG is almost double in sleep deprivation EEG than that of routine EEG. Whether this long duration of recording in sleep deprived cases has given much more abnormal EEG than that of others and whether sleep deprived EEG should b...
With great interest we have read the research paper by Kingwell et al. on cancer risk with interferon-beta (IFNb) treatment in MS. The authors cautiously conclude that a possible association between IFNb usage and the occurrence of breast cancer should be investigated further. Although the authors interpret their overall finding as reassuring that overall cancer risk does not seem to be increased in IFNb users, they disc...
Dear Editor,
I read with interest the article by Yogarajah et al 1. Working in a comprehensive epilepsy center of a tertiary referral hospital in the United States, I found the cost benefit analysis of long term monitoring (LTM) either by video telemetry (VT) or inpatient ambulatory electroencephalography (aEEG) useful information indeed. I agree with the authors that one of the greatest utility of LTM lies in...
Dear Editor
Baurmann was the first to explain the physilogical conditions of the central retinal venous pulse (collapse). We reassessed the experimental setting by a new technical model. We could confirm the results of Baurmann. The experiment as well as clinical investigations show that venous collapse can be used to exactly measure the intravasal pressure in the outflow vein (therefore we created the term - venou...
We write in relation to the editorial commentary from Khan et Tselis (1) who rightly suggest caution to consider chronic cerebrospinal venous insufficiency (CCSVI) as a pathological entity and cast serious doubt on its relevance to multiple sclerosis (MS); they forecast properly designed studies to investigate the relevance of CCSVI to MS, in order to carry out interventional procedures. The absence of extracranial venous...
Pages