I read the article by Zivadinov (1) with reference to the association
of Epstein-Barr virus (EBV) to gray matter atrophy in multiple sclerosis
(MS) patients.
Accumulation of EBV infected B cells in meninges and perivascular
regions of MS lesions in 21 or 22 patients with MS (2) was noted as well,
indicating direct involvement of the brain and perivascular spaces by EBV
in MS patients.....
I read the article by Zivadinov (1) with reference to the association
of Epstein-Barr virus (EBV) to gray matter atrophy in multiple sclerosis
(MS) patients.
Accumulation of EBV infected B cells in meninges and perivascular
regions of MS lesions in 21 or 22 patients with MS (2) was noted as well,
indicating direct involvement of the brain and perivascular spaces by EBV
in MS patients..
A recent study has indicated chronic cerebrospinal venous
insufficiency with multiple extracranial venous strictures in MS patients
(3).
EBV appears to infect endothelial cells (4), and may be important in
the pathology of EBV virus.
EBV virus has been found to cause deep venous thrombosis in a patient
with hereditary thrombophilia (5).
EBV may infect the venous endothelium causing venous thromboses and
strictures in the cranial and spinal venous drainage system and
perivascular regions of MS lesions in patients with MS.
Such venous involvement may be implicated in MS disease involvement.
Chronic EBV infection may involve the venous system with secondary
effects on the brain and spinal cord in MS.
References
1.Zivadinov R, Zorzon M, Weinstock-Guttman B, Serafin M, Bosco A,
Bratina A, et al. Epstein-Barr virus is associated with grey matter
atrophy in multiple sclerosis
J Neurol Neurosurg Psychiatry 2009; 80: 620
-625.
2.Serafani B, Rosicarelli B, Franciotta D, et al. Dysregulated
Epstein-Barr virus infection in the multiple sclerosis brain.
J Exp Med
2007; 204:2899-2912.
3. Zamboni P, Galeotti P, Menegatti E, Malagoni AM, Tacconi G, et
al. Chronic cerebrospinal venous insufficiency in patients with multiple
sclerosis.
J Neurol Neurosurg Psychiatry 2009: 80: 392-398.
4. Jones K, Rivera C, Sgadari C, Franklin J, Max EE, et al. Infection of human endothelial cells with Epstein-Barr virus.
J Exp Med.
1995; 182: 1213-1221.
5. Mashav N, Saar N, Chundadze T, Steinvil. Epstein-Barr virus
associated thromboembolism: A case report and review of the literature.
Thromb Res. 2008; 122: 570-571.
With interest we read the article by Jann et al. on 16 patients with
diabetic mellitus (DM) who also developed chronic inflammatory
demyelinating polyneuropathy (CIDP) [1]. The study raises concerns.
Though it is stated that CIDP was diagnosed according to the criteria
of the American Academy of Neurology (AAN) [2,3], the authors define
partial conduction block and abnormal temporal dispers...
With interest we read the article by Jann et al. on 16 patients with
diabetic mellitus (DM) who also developed chronic inflammatory
demyelinating polyneuropathy (CIDP) [1]. The study raises concerns.
Though it is stated that CIDP was diagnosed according to the criteria
of the American Academy of Neurology (AAN) [2,3], the authors define
partial conduction block and abnormal temporal dispersion at variance from
what is recommended by the AAN [2]. According to the AAN criteria partial
conduction block (CB) is defined as >20% drop in negative peak area or
peak-to-peak amplitude plus <15% change in duration of the negative
peak between proximal and distal sites (partial CB) or >15% change in
duration between proximal and distal sites (possible CB/temporal
dispersion) [2].
How to explain that none of the 16 patients with CIDP had sensory
disturbances at the first examination but all had reduced sensory nerve
conduction velocity of the median and sural nerves and severe loss of
myelinated fibres and macrophage infiltration and nine T-cell infiltration
on sural nerve biopsy?
Assessment of the clinical reaction to intravenous immunoglobulines
(IVIG) by the neuropathy impairment score (NIS) is misleading, since the
NIS predominantly scores motor functions [4], as admitted. Since eight of
the 16 developed sensory disturbances, including paresthesias, during
follow-up and since the summed sensory action potential (SAP) amplitude of
the sural and median nerve decreased during the 40m follow-up, the overall
results may be false positive.
Was the reduction of the SAP-amplitude particularly found in the
eight patients who developed sensory disturbances under IVIG?
Was the development of sensory disturbances attributed to worsening
diabetic polyneuropathy or to non-responding CIDP? How can the development
of sensory abnormalities be attributed to superimposed diabetic
polyneuropathy if the glycaemic control was excellent?
Which was the reason why two of the 16 did not respond to IVIG at
all? How often were IVIG in these two patients administered before they
were classified as non-responders? Which were the criteria according to
which they were classified as non-responders?
Except for two patients all others received IVIG repeadetly. Which
were the criteria to repeat the treatment?
How many patients had renal insufficiency before IVIG and in how many
did renal insufficiency worsen after IVIG?
In the method section also the ulnar nerve is mentioned to have been
investigated. Which is the reason why no results of this nerve are
presented?
How to explain the marked male preponderance among CIDP patients
(male/female: 13/3)?
As long as these concerns are not fully addressed there remain doubts
about the study results in particular the effectiveness of IVIG in
diabetic patients who also develop CIDP.
References
1. Jann S, Bramerio MA, Facchetti D, Sterzi R. Intravenous
immunoglobulin is effective in patients with diabetes and with chronic
inflammatory demyelinating polyneuropathy: long term follow-up. J Neurol
Neurosurg Psychiatry 2009;80:70-3.
2. Cornblath DR, Feasby TE, Hahn AF, et al. Research criteria for
diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Neurology 1991;41:61718.
3. Sander HW, Latov N. Research criteria for defining patients with
CIDP. Neurology 2003;60(suppl 3):S8-15.
4. Dyck PJ, Davies JL, Litchy WJ, O'Brien PC. Longitudinal assessment
of diabetic polyneuropathy using a composite score in the Rochester
Diabetic Neuropathy Study cohort. Neurology 1997;49:229-39.
In their recent publication of the updated prevalence and incidence
of multiple sclerosis (MS) in South East Wales, Hirst et al. reported a
significant increase of the MS prevalence from 101 / 105 to 146 / 105
(definite and probable MS) in the last twenty years (1). Although the rate
is signigicantly higher at present and the MS incidence had increased
continuously since the first survey, one might...
In their recent publication of the updated prevalence and incidence
of multiple sclerosis (MS) in South East Wales, Hirst et al. reported a
significant increase of the MS prevalence from 101 / 105 to 146 / 105
(definite and probable MS) in the last twenty years (1). Although the rate
is signigicantly higher at present and the MS incidence had increased
continuously since the first survey, one might be careful with a definite
conclusion: improved diagnostic facilities and increased public awareness
have also impact on MS incidence, and the - by definition – always lower
number of incident cases result in greater confidence intervals. The MS
prevalence, however, is still lower than in different areas in Scotland
(2), particularly in the Orkneys and Shetland, which are still one of the
highest-risk areas in the world. Although the genetic background of both
populations also differ (1), the search for environmental causes is
justified.
In an earlier publication I had focussed on the particularly high
risk of MS when peat is used by the population for burning purposes, in
particular for the smoking of meat for its preservation (3). Peat was used
in Wales for a long time in history (4). The situation was similar, but
not identical to Scotland, the other peat-rich region in the UK. In
contrast to Scotland, two larger coal fields occurred in Wales, and the
simultaneousd use of coal, peat and even wood for burning was shown on a
map in North Wales (4), demonstrating the situation in the late 17th
century.
In one of the earliest epidemiological papers in the UK, Allison had
studied five counties of North Wales, and found an overall MS prevalence
of 11.65 / 105 in 1932, which is not unusual for that time. The
distribution of cases, however, was unrandom, with a paticularly high rate
on the island of Anglesey, where 25% of MS cases vs. 10% of the population
(5) was living. In his treatise on the history of peat-cutting and fuel
supply in Wales, T.M.Owen (4) emphasised the mixed fuel supply (peat;
coal; wood) in many regions of Wales, and the delivery of coal was
considerably facilitated by the construction of the railroad in the middle
of the 19th century. On the island of Anglesey, however, due to the almost
lack of coal and the much later construction of railroads after 1950, peat
usage for burning was particularly high in the 19th century (4), and may
have lasted until the 20th .
It is interesting to note that early descriptions of the Shetland
Islands reported exclusively the preservation of fish and mutton by wind-
drying in so-called 'skeos', providing the unsalted 'vivda' and the salted
'blowen meat' and 'blowen fish', which were commonplace among the
population until ca. 1800 (6,7). Skeos were built from stone with openings
for the passage of wind, very similar to Faroese 'hjállur' built from
wood, but having otherwise the same purpose. The latter are still in
extensive use (7; own observation), in contrast to the Shetlands, were
they got into complete oblivion in the course of the 19th century, and the
present difference in the MS prevalence between both island groups shall
be mentioned in that context. Preservation of fish and mutton in Shetland
was replaced by smoking and smoke-drying in the cottages ('reesting') for
weeks and months (7,8) over an ever-burning peat fire, and in some
cottages this method is still practiced today (7). The old preservation
method by long-term drying in the air, however, shall be revived by
efforts of the Shetlands Livestock Marketing Group (7). If peat used for
that purpose is, in fact, on the decline, and if this is one reason for
the falling incidence of MS in Shetland (9), is an open question that
might be studied in detail.
References
1. Hirst C, Ingram G, Pickersgill T, Swingler R, Compston DAS,
Robertson NP. Increasing prevalence and incidence of multiple sclerosis in
South East Wales. J Neurol Neurosurg Pysychiatry 2009;80:386-391.
2. Forbes RB, Swingler RJ. Estimating the prevalence of multiple
sclerosis in the United Kingdom by using capture-recapture methodology. Am
J Epidemiol 1999;149:1016-1024.
3. Lauer K. The frequency of multiple sclerosis in high-risk areas: a
possible association with peat. J Neurol 1994;241 (Suppl 1): 7.
4. Owen TM. Historical aspects of peat-cutting in Wales. In: Jenkins
G (ed.) Studies in folk life. New York: Arno Press, 1977: 123-155.
5. Allison RS. Disseminated sclerosis in North Wales. Brain
1930;53:391-430.
6. Hibbert S. A description of the Shetland Islands, comprising an
account of their geology, scenery, antiquities, and superstitions. Edinburgh: Archibald Constable and Co., 1822.
It is important to note more than half of the patients of dementia
are not started on any of anti-dementia drugs at first evaluation (866-
56.4%) and nearly 40% of patients not received even after one year of
follow up.
Even though there is not much difference in clinical condition,
cognitive status behavioral and psychological symptoms between the patents
with and without any treatment (table 2...
It is important to note more than half of the patients of dementia
are not started on any of anti-dementia drugs at first evaluation (866-
56.4%) and nearly 40% of patients not received even after one year of
follow up.
Even though there is not much difference in clinical condition,
cognitive status behavioral and psychological symptoms between the patents
with and without any treatment (table 2) it is interesting to know that
about half (49% , table2) are admitted into nursing homes as compared to
only 21% of ChEI and 5% of ChEi + memantine group patients, it is unclear
why they seek nursing care or it may be due to treatment seeking behavior
of the care givers of these patients.
The mean follow up duration of patients with both memantine and
ChEI (Table 2) appears have much lower compared to patients with only
ChEI. It is also important to note that more percentage of medical illness
among only ChEI group than on combi group.
In response to B.Boucher's interesting question of whether we found
smoking to be associated with worsened cognitive performance at higher
serum 25-(OH)D concentrations than would be the case in non-smokers...
1. Although smokers had lower PTH levels than non-smokers (ca. 0.1
SD), this difference was non-signifcant following adjustment for age.
In response to B.Boucher's interesting question of whether we found
smoking to be associated with worsened cognitive performance at higher
serum 25-(OH)D concentrations than would be the case in non-smokers...
1. Although smokers had lower PTH levels than non-smokers (ca. 0.1
SD), this difference was non-signifcant following adjustment for age.
2. We found no evidence of a 25(OH)D*smoking status interaction
effect in fully adjusted models, i.e., smokers performed worse on the DSST
test irrespective of 25(OH)D levels compared to non-smokers.
3. We are unable to determine the presence of any dose-dependent
effects re: smoking as we collected this data in the form of current-,
past, and non-smoker only.
I read the article by Zomboni (1) with interest, with respect to the
interaction of the cerebral venous system and central nervous system in
development of multiple sclerosis (MS).
An interaction between the central nervous system and venous system
has been observed previously in MS lesions by F. A Schelling (2) who
initially observed “striking widening of the main venous passageways in
t...
I read the article by Zomboni (1) with interest, with respect to the
interaction of the cerebral venous system and central nervous system in
development of multiple sclerosis (MS).
An interaction between the central nervous system and venous system
has been observed previously in MS lesions by F. A Schelling (2) who
initially observed “striking widening of the main venous passageways in
the skulls of victims of multiple sclerosis”, and observed venous
involvement in the development of cerebral lesions of multiple sclerosis.
His supposition was lesions of MS are due to venous back jets from
intermittent rises in pressure in the large collecting veins of the neck
and especially the chest (2) and noted that Beno Schlessinger, in 1939,
while injecting the straight sinus under heavy pressure, noted the
extravasations produced around the lateral ventricles “closely stimulate
the distribution and even shapes of plaques in multiple sclerosis”.
Certainly venous involvement is distinctive in MS plaques, which
usually are perivenous in location, especially in the brain.
The venous outflow obstructions noted by Zamboni (1) appear
significant in the development of multiple sclerosis, however their origin
remains uncertain. Possibly they are developmental, although an underlying
abnormality of the venous wall could also lead to development, especially
since MS more commonly develops during adult life, and possibly there is
more than one etiology since MS is variable in symptomatology.
Venous obstruction may lead to decreased cerebrospinal fluid
reabsorption with subsequent toxicity to neuronal structures from retained
CSF components. Additional injury would occur subsequent to breakdown of
the blood brain barrier from intermittent elevation of venous pressure
injuring capillary and venule endothelium, with secondary development of
autoimmunity to brain components following exposure to the systemic immune
system, which is ordinarily barred from the central nervous system. After
autoimmunization to brain components, MS could transition from a initial
abnormality of venous drainage to a secondarily progressive autoimmune
disease.
References
1. P Zamboni, R Galeotti, E Menegatti, et al. Chronic cerebrospinal
venous insufficiency in patients with multiple sclerosis.
J Neurol
Neurosureg Psychiatry 2009; 80: 392-399.
2. F Alfons Schelling MD Multiple sclerosis: The image and its
message. The meaning of the classic lesion forms.
Available on line at
URL: http://www.ms-info.net/ms_040504.pdf
Congratulations to Fowler et al on publishing UK consensus on the
bladder management in Multiple sclerosis1. This timely publication will be
welcomed by all the health care professionals dealing with patients with
MS.
The common cause of bladder dysfunction in MS is lesions in the
spinal cord. The pathogenesis of bladder symptoms in MS are similar to
that of people with incomplete Spinal...
Congratulations to Fowler et al on publishing UK consensus on the
bladder management in Multiple sclerosis1. This timely publication will be
welcomed by all the health care professionals dealing with patients with
MS.
The common cause of bladder dysfunction in MS is lesions in the
spinal cord. The pathogenesis of bladder symptoms in MS are similar to
that of people with incomplete Spinal Cord injuries. Authors of UK
consensus statement commended that upper tract complications are much less
common in people with MS than in people with Spinal cord injuries1. While
hydronephrosis and renal failure may be rare in people with MS , they
often develop urinary tract stones. de Seze et al recommends annual
ultrasound examination of bladder in people with MS2. Wan et al noted that
17% of people with neurogenic bladder and upper tract stones, had
multiple sclerosis 3. Sliwa et al found significant upper tract
abnormalities on ultrasound in 21% of people with MS with bladder
symptoms4. Lemack et al found abnormalities in upper urinary tracts on
ultrasound examination in 16.7% of people with MS5.
The UK consensus statement has not made any mention of regular
ultrasound examination to screen for upper tract problems in people with
MS. Ultrasound is not an invasive test. It can also be used for estimation
of the residual urine. In my opinion people with MS and bladder symptoms
should have annual ultrasound examination of kidney, ureter and bladder.
References
1. Fowler CJ, Panicker JN, Drake M et al. A UK consensus on the
management of the bladder in multiple sclerosis.
J Neurol Neurosurg
Psychiatry 2009; 80: 470-477.
2. de Seze M, Ruffion A, Denys P et al. The neurogenic bladder in
multiple sclerosis: review of the literature and proposal of management
guidelines.
Mult Scler 2007; 13: 915-928.
3.Wan J, Fleenor S, Kielczewski P et al. Urinary tract status of
patients with neurogenic dysfunction presenting with upper tract stone
disease.
J Urol 1992; 148: 1126-1128.
4.Lemack GE, Hawker K, Frohman E. Incidence of upper tract
abnormalities in patients with neurovesical dysfunction secondary to
multiple sclerosis:analysis of risk factors at initial urological
evaluation.
Urology 2005;65:854-857.
5. Sliwa JA, Bell HK, Mason KD, et al. Upper tract abnormalities in
multiple sclerosis patients with urinary symptoms.
Arch Phys Med Rehabil
1996; 77:247-251.
This study suggest that electrical somatosensory stimulation may
improve motor function of the affected hand after stroke. There are very
few therapeutic options for the treatment of motor disabilities from
stroke. Motor training results in use-dependent plasticity, thought to
underlie recovery of motor function after cortical lesions. Use-dependent
plasticity (UDP) is instrumental in motor learnin...
This study suggest that electrical somatosensory stimulation may
improve motor function of the affected hand after stroke. There are very
few therapeutic options for the treatment of motor disabilities from
stroke. Motor training results in use-dependent plasticity, thought to
underlie recovery of motor function after cortical lesions. Use-dependent
plasticity (UDP) is instrumental in motor learning and may play a role in
recovery of function after brain lesions. The influence of somatosensory
input potentiates plastic changes associated with use in stroke patients.
Stimulation of the somatosensory cortex enhanced excitatory postsynaptic
potentials in the motor cortex,and stimulation of muscle, tactile, and
joint afferents activate motor cortical areas. This study brings a new
hope for better care of post stroke disability.
I read with interest the article by Moddel et al. about the efficacy
of intravenous levetiracetam in the treatment of refractory status
epilepticus 1. Their retrospective chart review of 36 patients treated
with intravenous levetiracetam suggests that it may be a safe and
efficacious treatment for refractory status epilepticus and adds to the
existing literature for this off label use. I commend th...
I read with interest the article by Moddel et al. about the efficacy
of intravenous levetiracetam in the treatment of refractory status
epilepticus 1. Their retrospective chart review of 36 patients treated
with intravenous levetiracetam suggests that it may be a safe and
efficacious treatment for refractory status epilepticus and adds to the
existing literature for this off label use. I commend the authors for this
useful information but have some comments. Patients had failed at least
one other antiepileptic drug prior to bolus loading of intravenous
levetiracetam leading to termination of status epilepticus in the majority
of patients within 24 hours. For termination of status epilepticus a
combination of drugs with different mechanisms of action acting
synergistically is preferred and it is possible that status epilepticus
would have been terminated in the majority of patients, irrespective of
the choice of antiepileptic drug employed next. There is no doubt that
intravenous levetiracetam by virtue of its favorable side-effect profile
is a very useful addition to our exiting armament for treating refractory
status epilepticus. Its efficacy though remains unproven and till further
information is available it may be wise to adhere to the conventional
status epilepticus abatement protocol of benzodiazepine->phenytoin-
>phenobarbital followed by either midazolam, propofol or pentobarbital
infusion.
References
1. Möddel G, Bunten S, Dobis C, Kovac S, Dogan M, Fischera M, Dziewas
R, Schäbitz WR, Evers, Happe S. Intravenous levetiracetam: a new
treatment alternative for refractory status epilepticus.
J Neurol
Neurosurg Psychiatry 2009; 80: 689-692.
This interesting paper adjusts for smoking and smoking reduces
circulating parathyroid hormone concentration; this effect would be
expected to reduce vitamin D activation(1). One might, therefore, expect
smoking to be associated with worsened cognitive performance at a higher
serum 25-(OH)D concentration than would be the case in non-smokers. Can
the authors tell us, therefore, whether there is any...
This interesting paper adjusts for smoking and smoking reduces
circulating parathyroid hormone concentration; this effect would be
expected to reduce vitamin D activation(1). One might, therefore, expect
smoking to be associated with worsened cognitive performance at a higher
serum 25-(OH)D concentration than would be the case in non-smokers. Can
the authors tell us, therefore, whether there is any such difference in
relation to smoking and, in particular, whether there may be dose-effects
with numbers of cigarettes smoked per day as may be the case for
reductions in serum PTH (Boucher BJ, 2001, Letter to Brit J Nutr)?
PS. Recent references available on this effect of smoking if
required. BJB
Dear Editor,
I read the article by Zivadinov (1) with reference to the association of Epstein-Barr virus (EBV) to gray matter atrophy in multiple sclerosis (MS) patients.
Accumulation of EBV infected B cells in meninges and perivascular regions of MS lesions in 21 or 22 patients with MS (2) was noted as well, indicating direct involvement of the brain and perivascular spaces by EBV in MS patients.....
Dear Editor,
With interest we read the article by Jann et al. on 16 patients with diabetic mellitus (DM) who also developed chronic inflammatory demyelinating polyneuropathy (CIDP) [1]. The study raises concerns.
Though it is stated that CIDP was diagnosed according to the criteria of the American Academy of Neurology (AAN) [2,3], the authors define partial conduction block and abnormal temporal dispers...
Dear Editor,
In their recent publication of the updated prevalence and incidence of multiple sclerosis (MS) in South East Wales, Hirst et al. reported a significant increase of the MS prevalence from 101 / 105 to 146 / 105 (definite and probable MS) in the last twenty years (1). Although the rate is signigicantly higher at present and the MS incidence had increased continuously since the first survey, one might...
Dear Editor,
It is important to note more than half of the patients of dementia are not started on any of anti-dementia drugs at first evaluation (866- 56.4%) and nearly 40% of patients not received even after one year of follow up.
Even though there is not much difference in clinical condition, cognitive status behavioral and psychological symptoms between the patents with and without any treatment (table 2...
Dear Editor,
In response to B.Boucher's interesting question of whether we found smoking to be associated with worsened cognitive performance at higher serum 25-(OH)D concentrations than would be the case in non-smokers...
1. Although smokers had lower PTH levels than non-smokers (ca. 0.1 SD), this difference was non-signifcant following adjustment for age.
2. We found no evidence of a 25(OH)D...
Dear Editor,
I read the article by Zomboni (1) with interest, with respect to the interaction of the cerebral venous system and central nervous system in development of multiple sclerosis (MS).
An interaction between the central nervous system and venous system has been observed previously in MS lesions by F. A Schelling (2) who initially observed “striking widening of the main venous passageways in t...
Dear Editor,
Congratulations to Fowler et al on publishing UK consensus on the bladder management in Multiple sclerosis1. This timely publication will be welcomed by all the health care professionals dealing with patients with MS.
The common cause of bladder dysfunction in MS is lesions in the spinal cord. The pathogenesis of bladder symptoms in MS are similar to that of people with incomplete Spinal...
Dear Editor,
This study suggest that electrical somatosensory stimulation may improve motor function of the affected hand after stroke. There are very few therapeutic options for the treatment of motor disabilities from stroke. Motor training results in use-dependent plasticity, thought to underlie recovery of motor function after cortical lesions. Use-dependent plasticity (UDP) is instrumental in motor learnin...
Dear Editor,
I read with interest the article by Moddel et al. about the efficacy of intravenous levetiracetam in the treatment of refractory status epilepticus 1. Their retrospective chart review of 36 patients treated with intravenous levetiracetam suggests that it may be a safe and efficacious treatment for refractory status epilepticus and adds to the existing literature for this off label use. I commend th...
Dear Editor,
This interesting paper adjusts for smoking and smoking reduces circulating parathyroid hormone concentration; this effect would be expected to reduce vitamin D activation(1). One might, therefore, expect smoking to be associated with worsened cognitive performance at a higher serum 25-(OH)D concentration than would be the case in non-smokers. Can the authors tell us, therefore, whether there is any...
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