I read the article by Schmidt (1) with interest with respect to the
effects of memantine on multimodal imaging in Alzheimer’s disease.
The results of the study indicated some possible beneficial effects
of memantine treatment after a year, however the volumetric studies did
not reach statistical significance which would indicate effects of
treatment were uncertain with respect to imaging...
I read the article by Schmidt (1) with interest with respect to the
effects of memantine on multimodal imaging in Alzheimer’s disease.
The results of the study indicated some possible beneficial effects
of memantine treatment after a year, however the volumetric studies did
not reach statistical significance which would indicate effects of
treatment were uncertain with respect to imaging studies.
Reviewing the clinical scales utilized, although it was noted the 52
week decline was slower in the treated than the placebo patients, the ADCS
-ADL or Alzheimer Disease Cooperative Study-Activities of Daily Living
scale decline was 5.1 in memantine treatment and placebo non-treatment
groups, would indicate actual decline in daily living activities,
utilizing a widely utilized scale, was the same whether treated with
memantine or not.
The possible preservation of glucose metabolism and reduction in
decline of hippocampal volume loss in the treatment groups, while
encouraging with respect to effects of memantine, may have little effect
on the actual clinical progression of the disease, when the decline in the
activities of daily living scale is taken into consideration.
It appears the chemical shift imaging is technically difficult due
patient movement, which probably is related to dementia in the study
population.
Certainly such chemical shifting imaging would be of interest in assessing
the results of treatment.
An investigation involving plasma or blood sampling might be
preferable, to avoid the difficulties of movement sensitive imaging of the
brain in Alzheimer disease patients.
Assessing plasma signaling proteins might have some potential in such
investigations since they have been found to identify patients with mild
cognitive impairment who progressed to Alzheimer’s disease with about 90 %
accuracy when an array of 18 different signaling proteins is analyzed (2).
There was found to be disruption of hematopoiesis, immune responses,
apoptosis and neuronal support in such cases, which may indicate multiple
systems are breaking down in Alzheimer disease, which probably is not
identical in all patients.
Normalization of plasma signaling proteins monitored during treatment
might indicate correction of underlying cellular dysfunction.
References
1. Schmidt R, Ropele S, Pendl B. Et al. Longitudinal multimodal
imaging in mild to moderate Alzheimer disease: a pilot study with
memantine.
J Neurol Neurosurg Psychiatry. 2008; 79: 1212-1217.
2. Sandip R, Britschgi M, Herbert C, et al. Classification and
prediction of clinical
Alzheimer’s diagnosis based on plasma signaling proteins.
Nature Med.
2007; 13: 1359-1362.
We read the above study with interest and appreciated the thorough
analysis. Whilst the authors acknowledge in their discussion that the Wada
test is a 'silver standard', they nevertheless conclude that the Wada test
is warranted when fMRI fails to show clear left lateralisation. We would
make the following points:
1. The true "gold standard" for language dominance tests is
prediction of outc...
We read the above study with interest and appreciated the thorough
analysis. Whilst the authors acknowledge in their discussion that the Wada
test is a 'silver standard', they nevertheless conclude that the Wada test
is warranted when fMRI fails to show clear left lateralisation. We would
make the following points:
1. The true "gold standard" for language dominance tests is
prediction of outcome. The authors acknowledge this in their discussion.
2. Recent studies suggest that high-quality fMRI is somewhat more
accurate than the Wada test in predicting postoperative language outcomes.
Sabsevitz et al showed better prediction of naming outcome by fMRI than by
Wada in an unselected sample of left anterior temporal lobectomy patients.
Janecek et al demonstrated that in patients with discordant fMRI and Wada,
fMRI is generally more accurate at predicting language outcomes than the
Wada test. Thus it is erroneous to consider fMRI results as inaccurate
simply because the technique picks up more activation in the right
hemisphere. It turns out that this "non-essential activation" probably
helps patients recover.
3. For these reasons, it makes little sense to use fMRI as a
screening tool and Wada as the standard in patients with atypical language
representation.
4. The conclusion that the Wada test is warranted cannot be justified
using this methodology employing a suboptimal clinical standard.
References:
Sabsevitz DS, Swanson SJ, Hammeke TA, Spanaki MV, Possing ET, Morris
GL, Mueller WM, Binder JR. Use of preoperative functional neuroimaging to
predict language deficits from epilepsy surgery. Neurology, 2003; 60: 1788
-1792.
Janecek JK, Swanson SJ, Sabsevitz DS, Hammeke TA, Raghavan M, Mueller
W, Binder JR. Naming outcome prediction in patients with discordant Wada
and fMRI language lateralization. Epilepsy & Behavior, 2013; 27: 399-
403.
The synthesis of epidemiological studies of the natural history of
treated and untreated epilepsy proposed in 2004 by Kwan and Sander(1)
separates people with epilepsy into 3 prognostic groups. However, further
interpretation of available evidence suggest that this prognostic groups
could be further subdivided:
Group 1 is the group of patients who would enter remission with or
without an...
The synthesis of epidemiological studies of the natural history of
treated and untreated epilepsy proposed in 2004 by Kwan and Sander(1)
separates people with epilepsy into 3 prognostic groups. However, further
interpretation of available evidence suggest that this prognostic groups
could be further subdivided:
Group 1 is the group of patients who would enter remission with or
without antiepileptic drug (AED) therapy, those who would automatically
achieve remission even if they did not have access to AEDs.
Sub-Group 1A therefore will represent those with immediate
spontaneous remission. They will not have a third seizure, i.e. upon
starting AED or being recruited into a cohort, they enter remission
immediately, and will not relapse after complete AED withdrawal. In a New
York childhood first seizure cohort, Shinnar et al(2) reported that out of
182 children who had a second seizure, 28% did not have a third seizure
(second recurrence) at 5 years follow up, meaning they could be
effectively considered as having entered into immediate remission.
Hauser et al(3) reported that 27% did not have a second recurrence
after 4 years of follow up in an all age cohort in Minnesota. Treatment
did not influence the rate of second recurrence in both studies, although
for Hauser et al(3) the risk of additional seizures in those with two
previous seizures is greater than the risk of adverse effects of
antiepileptic drugs. Neither study investigated the subset of these
patients who are successfully taken off antiepileptic drugs. Hence the
proportion of patients within IA may be less than they have reported.
Sub-Group 1B represents those who although do not enter remission
immediately, ultimately do so, and who alongside those who enter immediate
remission, will remain in remission on antiepileptic drug withdrawal.
There is however no study from which an estimate of the proportion of
patients who will be in this group could be derived. It does however
fulfil an important conceptual role within the range of temporal
prognostic epilepsy.
Notwithstanding their original eligibility into any of the Sub-Groups
of Group 1, those who cannot be successfully weaned off antiepileptic
drugs belong in Group 2. Those within Sub-Group 2A are patients whose
epilepsy alongside the whole of Group 1 did run a remitting course only
that they could not be taken off AED. Those in Sub-Group 2B arrived in
remission after a remitting-relapsing course. People in Sub-Group 2B made
up 20% of the Finnish cohort.(4)
Group 3 comprises those patients who will not enter terminal
remission either because after a remitting-relapsing course they do not
achieve terminal remission (14% of Sillanpaa et al's Finnish childhood
cohort) (4) or because they continue to have seizures from diagnosis in
spite of AEDs i.e. they never experience remission. Within this group will
be those (Sub-Group 3A) who will continue to have seizures, not frequent
or debilitating enough to be described as intractable and those (Sub-Group
3B) who will fulfil the definition of medically intractable seizures: 10%
in Berg et al's prospective population based cohort.(5)
Further subdivision of 3B would give us the two categories of those
whose seizures will remit on non-pharmacological intervention, and those
who will never achieve remission no matter the intervention. Sub-Group 3A
will also have a sub-population of those who ran a remitting-relapsing
course within it. Therefore the whole of Sub-Group 2B and part of Sub-
Group 3A is made of patients running a remitting-relapsing course, which
also indicates that the boundary between Sub-Group 2B and Sub-Group 3A
will be a potential area of cross-over activity.
One group that may exist but is not covered here is that of patients
who initially enter immediate remission and then go on to have a remitting
-relapsing course, but are eventually successfully weaned off AEDs.
However, evidence from Sillanpaa et al(4) suggest that it is unlikely that
such individuals exist. They show that the number of years before entering
5-year remission is an independent predictor of relapse. Therefore there
is a low probability that a patient with immediate remission will go on to
have a remitting-relapsing course, and if they do, it may be ill advised
to wean them off AEDs.
References
1. Kwan P, Sander JW. The natural history of epilepsy: an
epidemiological view. Journal of Neurology, Neurosurgery & Psychiatry.
2004 Oct;75(10):1376-81.
2. Shinnar S, Berg AT, O'Dell C, Newstein D, Moshe SL, Hauser WA.
Predictors of multiple seizures in a cohort of children prospectively
followed from the time of their first unprovoked seizure. Annals of
Neurology. 2000 Aug;48(2):140-7.
3. Hauser WA, Rich SS, Lee JR, Annegers JF, Anderson VE. Risk of
recurrent seizures after two unprovoked seizures. New England Journal of
Medicine. 1998 Feb 12;338(7):429-34.
4. Sillanpaa M, Schmidt D, Sillanpaa M, Schmidt D. Natural history of
treated childhood-onset epilepsy: prospective, long-term population-based
study. Brain. 2006 Mar;129(Pt 3):617-24.
5. Berg AT, Shinnar S, Levy SR, Testa FM, Smith-Rapaport S, Beckerman
B. Early development of intractable epilepsy in children: A prospective
study. Neurology. 2001;56(11):1445-52.
Reina and co-workers found no difference in morphological features of
mounted cadaveric dura mater and arachnoid membranes punctured by
disposable 22 gauge Quincke needle with the bevel either in the parallel
or in the transverse position.[1]
None of the factors linked to post-dural
puncture headache (PDPH) including young age, female sex with lower body
mass index, pregnancy or previous PDPH hi...
Reina and co-workers found no difference in morphological features of
mounted cadaveric dura mater and arachnoid membranes punctured by
disposable 22 gauge Quincke needle with the bevel either in the parallel
or in the transverse position.[1]
None of the factors linked to post-dural
puncture headache (PDPH) including young age, female sex with lower body
mass index, pregnancy or previous PDPH history[2-4] can be synthesized
into a logical hypothesis that predictably explains the particular
susceptibility of this sub-population. The concept that size of the dural
puncture and PDPH are directly related has evolved the consensus
recommendation to use thin, non-traumatic tip needle or the Quincke
needle.[4] This recommendation must, however, be balanced against the
failure of Tourtellotte et al. to show the relation between smaller needle
size and lower frequency of PDPH in their prospective series.[2] Remarkably,
Tourtellotte et al. also commented on:
(i) the great variability of PDPH
frequency for the same needle size between different authors;
(ii) the
lack of conclusive evidence regarding other risk factors; and
(iii)
variation in actual frequencies of PDPH in individual series ranging from
0 to 18%.[2] The more recent study of Kuntz et al. confirms that PDPH
continues to affect patients and concern neurologists.[3,4]
Unpredictable development of PDPH as well as the relative rarity of
the headache in spinal anesthesia, obstetric or non-obstetric,[2,4]
stimulates lateral thinking. With a “U” shaped or semi-lunar shaped dura-
arachnoid lesion (DAL) caused by the Quincke needle,[1] continuous
cerebrospinal fluid (CSF) leakage reflects failure of the clean cut edge
of the dural flap to effectively seal the DAL. Unlike the dura mater, the
inflamed arachnoid membrane can proliferate and is prominently adhesive,
which singular tissue properties underlie the frequent development of
lumbar spinal arachnoiditis. Whereas simple re-approximation of the cut
dural flap to its original position may not stop leakage of CSF, the
locally-traumatized and adhesive arachnoid probably seals spontaneously
most dural punctures. PDPH might, therefore, be consequential to failure
of the arachnoid to seal off the DAL. Quincke needles lessen but do not
eliminate the “tent effect” [1] that stretches both the dura mater as well
as the arachnoid membrane at the site of the DAL. Due to different
biomechanical and tensile properties, rupture of the arachnoid membrane
may not always follow the precise anatomical pattern of the dural hole
created during lumbar puncture (LP); also partial loss of arachnoid lamina
at the site of the DAL is possible. Variable degrees of retraction of the
arachnoid membrane at the site of the DAL, as can be seen in the scanning
electron microscope pictures presented by Reina et al,[1] may also
contribute to prolonged or persistent CSF leakage. If this explanation is
truly representative of the biomechanics of the DAL created by LP, use of
the same LP needle is unlikely to create identical DAL in different
patients; the unpredictability of PDPH in terms of incidence and duration
might thus be rationalized.
Low incidence of PDPH in spinal anesthesia 2 intriguingly suggests
that spinal anesthesia confers a degree of protection from PDPH.
Tourtellotte et al. speculated that the incidence of PDPH might be
markedly lessened if patients undergoing diagnostic LP were “treated” like
patients undergoing spinal anesthesia.[2] In this context, the clinical
circumstances surrounding the LP could also be important. Non-obstetric
spinal anesthesia is usually preceded by CT- myelograms (and MRI or both)
for evaluating underlying clinical conditions possibly correctable by
surgery. Myelography is associated with arachnoiditis.[5] Post-myelography,
the subclinically inflamed arachnoid may be primed to seal a subsequent
DAL more efficiently. Notably, Tourtellotte et al. found the lowest
incidence of PDPH for nonobstetric spinal anesthesia (average frequency
was 13%).[2]
Modification of patient-related risk factor(s) to reduce the
frequency of PDPH in patients undergoing diagnostic LP has been suggested.
4 No such modifiable factor is, however, currently known. Although the
mean CSF values for opening pressure, CSF cell count, and protein
concentration were all normal in 44 full-term pregnant women undergoing
spinal anesthesia for delivery,[6] pregnancy and the immediate postpartum
period are associated with the lowest CSF densities.[7] The less dense the
CSF, the greater are the chances of leakage through a DAL. Inducing
maximally tolerated dehydration to increase the viscosity of the CSF may
possibly reduce susceptibility of women undergoing obstetric spinal
anesthesia to develop PDPH. Moreover, dehydration aggravates severity of
arachnoiditis induced by aqueous myelography and fluid repletion is
recommended before myelography.[8] Paradoxically, dehydration prior to
obstetric spinal anesthesia or diagnostic LP may stimulate the arachnoid
lamina to seal the DAL more efficiently. Finally, the average frequency of
PDPH in obstetric spinal anesthesia was only 18%.[2] Endorphin activity in
CSF increases at term pregnancy,[9] indicating development of an adaptive
antinociception that possibly reduces incidence of PDPH.
References
1. Reina MA, López A, Badorrey V, De Andrés JA, Martin S. Dura-
arachnoid lesions produced by 22 gauge Quincke spinal needles during a
lumbar puncture. J Neurol Neurosurg Psychiatry 2004;75:893-7.
2. Tourtellotte WW, Haerer AF, Heller GL, et al. Post-lumbar puncture
headaches. Springfield, IL: Charles C. Thomas, 1964.
3. Kuntz KM, Kokmen E, Stevens JC, Miller P, Offord KP, Ho MM. Post-
lumbar puncture headaches: experience in 501 consecutive procedures.
Neurology 1992; 42: 1884–7.
4. Evans RW, Armon C, Frohman EM, et al. Assessment: prevention of
post–lumbar puncture headaches: report of the therapeutics and technology
assessment subcommittee of the American Academy of Neurology. Neurology
2000;55:909-14.
5. Eldevik OP, Haughton VM. Risk factors in complications of aqueous
myelography. Radiology 1978;128:415-6.
6. Davis LE. Normal laboratory values of CSF during pregnancy. Arch
Neurol 1979;36:443.
7. Richardson MG, Wissler RN. Density of lumbar cerebrospinal fluid
in pregnant and nonpregnant humans. Anesthesiology 1996;85:326-30.
8. Eldevik OP, Haughton VM. The effect of hydration on the acute and
chronic complications of aqueous myelography. An experimental study.
Radiology 1978;129:713-4.
9. Lyrenas S, Nyberg F, Willdeck-Lund G, Lindstrom L, Lindberg B,
Terenius L. Endorphin activity in cerebrospinal fluid prior to elective
cesarean section and in early puerperium. Ups J Med Sci 1987;92:37-45.
To G Tsivgoulis et al: I have read your paper thoroughly. You have concluded that higher casual and 24 hour pulse pressure during acute phase of stroke is associated with increase stroke recurrence and mortality at the end of first year, but you have not mentioned about duration of pre-stroke hypertension, severity of involvement or damage of other target organs such renal, eye, percent of carotid stenosis,...
To G Tsivgoulis et al: I have read your paper thoroughly. You have concluded that higher casual and 24 hour pulse pressure during acute phase of stroke is associated with increase stroke recurrence and mortality at the end of first year, but you have not mentioned about duration of pre-stroke hypertension, severity of involvement or damage of other target organs such renal, eye, percent of carotid stenosis, size of stroke etc.
Your study sample size is small (339 patients only). The study requires more patients for any conclusion. What was status of pulse pressure throughout the whole year? Was it constant or fluctuating to a large scale? According to guidelines for management of stroke, post-stroke blood pressure should be lowered when it is >220/120mm of Hg so that neurons of the ischemic penumbra can be saved. But according to your study, if high post-stroke PP is kept lower during acute phase of stroke it will help the patient – is it so? If yes, to what extent should it be lowered?
I read with interest the article by Whittaker et al. I
completely agree that the MRC scale is unsuitable for
detecting the small changes in strength seen in a slowly
progressive disease such as myotonic dystrophy (MD).
However, I also wonder what strength a hand-held dynamometers measure. MD is a disease that affects limb
muscles in the distal especially in hand muscles. Hand-held dynamometers may...
I read with interest the article by Whittaker et al. I
completely agree that the MRC scale is unsuitable for
detecting the small changes in strength seen in a slowly
progressive disease such as myotonic dystrophy (MD).
However, I also wonder what strength a hand-held dynamometers measure. MD is a disease that affects limb
muscles in the distal especially in hand muscles. Hand-held dynamometers may be heavy to hold for MD patients and
expensive. In our clinics, we use pinch meters to evaluate
the small changes in strength in MD disease course. I
consider that an optimal study to correlate results of
strength measured by hand-held dynamometers and pinch
meters is useful for developing standardizing method to
evaluate strength changes in MD patients.
In a recent, impressive article, Teruhiko Sekiguchi et al. (1)
hypothesize that misfolded proteins accumulating in some neurodegenerative
diseases, including Alzheimer's disease, Parkinson's disease, and
amyotrophic lateral sclerosis (ALS), can cause aggregation of their native
counterparts through a mechanism similar to the infectious prion protein's
induction of a pathogenic conformation onto its normal cellular isoform....
In a recent, impressive article, Teruhiko Sekiguchi et al. (1)
hypothesize that misfolded proteins accumulating in some neurodegenerative
diseases, including Alzheimer's disease, Parkinson's disease, and
amyotrophic lateral sclerosis (ALS), can cause aggregation of their native
counterparts through a mechanism similar to the infectious prion protein's
induction of a pathogenic conformation onto its normal cellular isoform.
Recent in vitro studies have indicated that newly formed aggregates of TAR
DNA-binding protein 43 as well as superoxide dismutase 1 (SOD1) can act as
templates for the subsequent misfolding of the respective native proteins,
and that the misfolded proteins can be intercellularly transferred in
cultured cells (2).
Neurodegeneration in ALS typically begins focally and then spreads
spatiotemporally until neurons of the respiratory system are lost. Some
researchers, therefore, suggest that ALS pathology is similarly initiated
at a single site and spreads via cell-to-cell transmission of prion-like
pathogenic conformers in a 'single seed and simple propagation' model of
ALS (2). Assuming that ALS progresses according to the proposed model, ALS
lesions will spread contiguously along the spinal segments. Using needle
electromyography (EMG), Sekiguchi et al. analyzed abnormal spontaneous
activity of pairs of muscles innervated from different spinal segments in
patients with early-stage sporadic ALS. They found that abnormal lower
motor neuron activity showed a noncontiguous pattern in many ALS patients,
suggesting that this skipping pattern of rostrocaudal spread does not
support the 'single seed' hypothesis. Instead, they proposed a 'multifocal
hits and local propagation' hypothesis. In their article, however, they do
not present the data to support their hypothesis of local disease spread
in a prion-like manner on the grounds that such data are not required from
a methodological point of view.
A motor pool refers to all of the individual motor neurons that
innervate a single muscle. Because of motor pools in the spinal cord are
clustered in distinct columns of motor neurons extending over multiple
spinal cord segments, a longitudinal study for estimating the number of
motor units from individual muscles in ALS patients may provide a
mechanistic insight into local disease spread.
Over the years a number of techniques have been developed to estimate
the number of motor units in humans by defining a motor unit as the spinal
motor neuron and its axon together with the muscle fibers it innervates.
Motor unit number estimation (MUNE) is a technique that uses EMG to
estimate the number of motor units in a muscle. Ridall PG et al.(3)
developed a Bayesian statistical methodology to analyze
electrophysiological data to provide an estimate of motor unit numbers.
This method uses mathematical equations that express the basic elements of
motor unit activation after electrical stimulation, allows for sources of
variability and uncertainty, and has the capacity to estimate a larger
number of motor units.
The exponential decimation of remaining lower motor neurons over time
and different rates of progression have recently been demonstrated using
the Bayesian MUNE (one of the most reliable methods for estimation of the
total number of motor units) in both ALS patients and SOD1-linked familial
ALS patients in all of the muscles examined (4). Furthermore, using SOD1
transgenic mice, MUNE values obtained with the Bayesian method showed a
solid correlation with the histologically determined number of remaining
lower motor neurons in the spinal cord. The exponential kinetics of
neuronal cell loss are consistent with the 'one-hit' model of
neurodegeneration described by Clarke et al. in which the death of a
neuron is initiated randomly in time by a single, rare, catastrophic event
independently of any neighboring neuron (5). Thus, the endogenous,
stochastic occurrence of the one-hit events in a homogenous population of
lower motor neurons may play a pivotal role in local disease spread. These
features are clearly distinct from those of the prion-like propagation
model of disease spread.
These findings, together with the study by Sekiguchi et al., suggest
that lower motor neuron dysfunction defined by the electrophysiological
evidence in ALS supports neither the 'simple propagation' nor the 'single
seed' hypothesis.
References:
1. Sekiguchi T et al. Spreading of amyotrophic lateral sclerosis
lesions--multifocal hits and local propagation? J Neurol Neurosurg
Psychiatry doi: 10.1136/jnnp-2013-305617
2. Polymenidou M, Cleveland DW. The seeds of neurodegeneration:
prion-like spreading in ALS. Cell 2011; 147:498-508.
3. Ridall PG, Pettitt AN, Henderson RD, McCombe PA. Motor unit
number estimation-a Bayesian approach. Biometrics. 2006; 62:1235-1250.
4. Baumann F et al. Quantitative studies of lower motor neuron
degeneration in amyotrophic lateral sclerosis: evidence for exponential
decay of motor unit numbers and greatest rate of loss at the site of
onset. Clin Neurophysiol. 2012; 123:2092-8.
5. Clarke G, Lumsden CJ. Scale-free neurodegeneration: cellular
heterogeneity and the stretched exponential kinetics of cell death. J
Theor Biol. 2005; 233:515-525.
In 2002, we reported in this journal a patient with corticosteroid-
responsive oculopharyngeal myopathy and an absence of chondroitin sulfate
in muscle biopsies [1]. In recent years, the patient was found to have
antibodies against muscle-specific kinase (MuSK). This female patient
presented in 1993 at the age of 42 years with proximal muscle weakness in
the neck and difficulty in swallowing, followed by blepharoptosis an...
In 2002, we reported in this journal a patient with corticosteroid-
responsive oculopharyngeal myopathy and an absence of chondroitin sulfate
in muscle biopsies [1]. In recent years, the patient was found to have
antibodies against muscle-specific kinase (MuSK). This female patient
presented in 1993 at the age of 42 years with proximal muscle weakness in
the neck and difficulty in swallowing, followed by blepharoptosis and
double vision. The symptoms showed no obvious diurnal variation with
normal repetitive stimulation tests and a negative Tensilon test, and
there was no thymoma. The patient developed respiratory failure associated
with hypercapnia and had to receive artificial respiration, but eventually
showed a dramatic recovery with oral corticosteroid therapy. The initial
diagnosis remained undetermined. Reports in the medical literature
describing corticosteroid-responsive myopathic cases with similar clinical
symptoms and signs associated with deficient chondroitin sulfate prompted
us to examine chondroitin sulfate in stored muscle specimens from the
patient and the results provided evidence for deficient chondroitin
sulfate [1,2]
In 2004, the patient had a worsening of her respiratory function
while given predonisolone orally at a dose of 12 mg/day. An increase of
predonisolone to 60 mg/day resulted in a marked resolution of the serious
symptoms, and this was followed by a gradual tapering of corticosteroids.
In 2008, a similar serious episode also induced a respiratory problem when
the patient was given predonisolone at a dose of 20 mg/day, in which an
increase of the dose to 60 mg/day again improved the symptoms. Thereafter,
predonisolone was gradually tapered to 30 mg/day as a maintenance dose.
Given the presence of similar symptoms in cases that were positive
for antibodies against MuSK [3], we examined the levels of these
antibodies in the patient's serum in 2008. We observed anti-MuSK
antibodies at a concentration of 10.0 nM (less than 0.01 nM in controls).
This high antibody titer led to a diagnosis of anti-MuSK antibody-positive
oculopharyngeal myopathy, although the patient did not have the clinical
features of myasthenia gravis. To the best of our knowledge, there are
only 2 cases, our current case and a previously reported case,
characterized by chondroitin sulfate-deficient myopathy [1,2].
The pathogenic relationship between deficient chondroitin sulfate and
anti-MuSK antibodies remains to be defined. It is possible that the
absence of chondroitin sulfate may involve an event that is secondary to
the myopathy associated with the presence of anti-MuSK antibodies. MuSK
forms a complex with several factors such as Dok7 [4]. Further studies are
necessary to examine whether chondroitin sulfate interacts with one of
these factors.
References
1. Yabe I, Kikuchi S, Higashi T, et al. A Japanese case of steroid
responsive myopathy with deficient chondroitin sulphate. J Neurol
Neurosurg Psychiatry 2002; 73: 89-90.
2. al-Lozi MT, Hemelt VB, Pestronk A. Steroid-responsive myopathy with
deficient chondroitin sulfate C in skeletal muscle connective tissue.
Neurology 1998; 50: 526-9.
3. Ohta K, Shigemoto K, Fujinami A, et al. Clinical and experimental
features of MuSK antibody positive MG in Japan. Eur J Neurol 2007; 14:
1029-34.
4. Bergamin E, Hallock PT, Burden SJ, et al. The cytoplasmic adaptor
protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization.
Mol Cell 2010; 39: 100-9.
We thank Dr Derakhshan for his comments [1] regarding our report.[2]
Dr Derakhshan discusses the hypothesis that all movements are initiated
from the major hemisphere,[3] which may be closely related to
handedness. In neural right handers, the command of movement may
originate in the left hemisphere. In cases of left hand movement, the
command originated from the dominant hemisphere is once tran...
We thank Dr Derakhshan for his comments [1] regarding our report.[2]
Dr Derakhshan discusses the hypothesis that all movements are initiated
from the major hemisphere,[3] which may be closely related to
handedness. In neural right handers, the command of movement may
originate in the left hemisphere. In cases of left hand movement, the
command originated from the dominant hemisphere is once transferred
to the right one via the corpus callosum, thereby producing the
movement.
Based on this hypothesis, Dr Derakhshan suggests that the left small
infarct in our case may have affected a command signal from the left to
the right hemisphere, thereby deteriorating the pre-existing left
hemiparesis that had resulted from an earlier right putaminal
haemorrhage. This discussion is interesting; however, we do not think
such hypothesis can fully explain the symptoms of our case. The first-
ever stroke in the dominant hemisphere rarely causes ipsilateral
hemiparesis or tetraparesis. Moreover, lesion of the corpus callosum
does not usually produce hemiparesis, which may be caused by the
inhibition of the command transfer from the major hemisphere to the
other one. In contrast, the deterioration of ipsilateral hemiparesis
appears to be seen in cases of the second stroke, which occurs
contralaterally to the first stroke. Thus, we feel that the reorganisation
of
motor control in the contralateral hemisphere after the first stroke may
play an important role in the deterioration of ipsilateral hemiparesis in
such cases.
On the other hand, side of stroke may considerably influence motor
recovery. In general, greater ipsilateral cortex recruitment is normally
seen with left compared with right hand movement in the right handers.
Such ipsilateral recruitment may increase further after brain damage.[4]
Thus, there may be increasing chances that left hemiparesis improves
better than right one because of the presence of the ipsilateral motor
control, and that, at the same time, pre-existing left hemiparesis
deteriorates when the second stroke takes place in the left hemisphere
like our case. Handedness and side of stroke should be taken into
consideration in discussing the process of motor recovery after stroke.
References
1. Derakhshan I. Making matters worse, ipsilaterally: A new explanation [electronic response to Ago et al. Deterioration of pre-existing hemiparesis brought about by subsequent ipsilateral lacunar infarction] jnnp.com 2004http://jnnp.bmjjournals.com/cgi/eletters/74/8/1152#133
2. Ago T, Kitazono T, Ooboshi H, et al. Deterioration of pre-existing
hemiparesis brought about by subsequent ipsilateral lacunar infarction. J
Neurol Neurosurg Psychiatry. 2003;74:1152-1153.
3. Kim SG, Ashe J, Hendrich K, et al. Functional magnetic resonance
imaging of motor cortex: hemispheric asymmetry and handedness.
Science. 1993;261:615-617.
4. Zemke AC, Heagerty PJ, Lee C, et al. Motor cortex organization
after
stroke is related to side of stroke and level of recovery. Stroke.
2003;34:e23-28.
The two objectives of the study conducted by Schmidt et al.(1) were
to test: A) the feasibility of multimodal imaging in Alzheimer’s disease
(AD); and B) the effects of memantine in AD. We were unclear as to why
the two objectives were not studied separately. Testing the feasibility
of multimodal imaging procedures may be clinically valuable. However, we
did not understand why it was necessary t...
The two objectives of the study conducted by Schmidt et al.(1) were
to test: A) the feasibility of multimodal imaging in Alzheimer’s disease
(AD); and B) the effects of memantine in AD. We were unclear as to why
the two objectives were not studied separately. Testing the feasibility
of multimodal imaging procedures may be clinically valuable. However, we
did not understand why it was necessary to conduct a randomised control
trial (RCT) for memantine at the same time, especially since it has
already been established that memantine treatments can give statistically
significant results with a minor clinical benefit(2,3). Therefore, we
question the clinical relevance of conducting RCT for memantine.
Additionally, we believe that exclusion of patients with
cerebrovascular disease and other medical conditions may have compromised
the study’s generalisability. We feel that AD population was not fairly
represented here as others(4, 5) demonstrate that 39-51% of AD patients
have associated co-morbidities (i.e. stroke, cardiovascular disease).
Finally, the abstract misleadingly reports significant p-values for
the total population rather than reporting non-significant statistical
values between the placebo and memantine groups for changes in glucose
metabolism and brain volume. Furthermore, we believe that the conclusions
may have been misleading in regards to overstating the decline in glucose
metabolism and hippocampal volume reduction. The authors concluded that
memantine has a potentially protective role in AD because both outcome
measures showed 40% lower annual decline (although not significant due to
low sample size). However, the absolute differences were 1.2% for glucose
metabolism and 1.6% for hippocampal volume reduction.
Disclosure: The authors report no conflict of interest.
References
1. R Schmidt, S Ropele, B Pendl, P Ofner, C Enzinger, H Schmidt, A
Berghold, M Windisch, H Kolassa, and F Fazekas. Longitudinal multimodal
imaging in mild to moderate Alzheimer disease: a pilot study with
memantine.
J Neurol Neurosurg Psychiatry 2008; 79: 1312-1317.
2. P Raina, P Santaguida, A Ismaila, C Patterson, C Cowan, D Levine,
L Mitchell, L Booker, Lynda, and M Oremus. Effectiveness of cholinesterase
inhibitors and memantine for treating dementia: evidence review for a
clinical practice guideline.
Annals of Internal Medicine. 2008; 148:379-
397.
3. R McShane , A Areosa Sastre, N Minakaran. Memantine for dementia.
Cochrane Database Syst Rev. 2006; 19:CD003154.
4. AD2000 Collaborative Group. Long-term donepezil treatment in 565
patients with Alzheimer's disease (AD2000): randomised double-blind trial.
Lancet 2004; 363:2105-2115
5. DW Desmond, JT Moroney, MC Paik, M Sano, JP Mohr, S Aboumatar, CL
Tseng, S Chan, JBW Williams, RH Remien, WA Hauser, and Y Stern. Frequency
and clinical determinants of dementia after ischemic stroke.
Neurology
2000; 54:1124–1131.
Dear Editor,
I read the article by Schmidt (1) with interest with respect to the effects of memantine on multimodal imaging in Alzheimer’s disease.
The results of the study indicated some possible beneficial effects of memantine treatment after a year, however the volumetric studies did not reach statistical significance which would indicate effects of treatment were uncertain with respect to imaging...
Dear Sirs,
We read the above study with interest and appreciated the thorough analysis. Whilst the authors acknowledge in their discussion that the Wada test is a 'silver standard', they nevertheless conclude that the Wada test is warranted when fMRI fails to show clear left lateralisation. We would make the following points:
1. The true "gold standard" for language dominance tests is prediction of outc...
Dear editor,
The synthesis of epidemiological studies of the natural history of treated and untreated epilepsy proposed in 2004 by Kwan and Sander(1) separates people with epilepsy into 3 prognostic groups. However, further interpretation of available evidence suggest that this prognostic groups could be further subdivided:
Group 1 is the group of patients who would enter remission with or without an...
Dear Editor
Reina and co-workers found no difference in morphological features of mounted cadaveric dura mater and arachnoid membranes punctured by disposable 22 gauge Quincke needle with the bevel either in the parallel or in the transverse position.[1]
None of the factors linked to post-dural puncture headache (PDPH) including young age, female sex with lower body mass index, pregnancy or previous PDPH hi...
Dear Editor,
To G Tsivgoulis et al: I have read your paper thoroughly. You have concluded that higher casual and 24 hour pulse pressure during acute phase of stroke is associated with increase stroke recurrence and mortality at the end of first year, but you have not mentioned about duration of pre-stroke hypertension, severity of involvement or damage of other target organs such renal, eye, percent of carotid stenosis,...
Dear Editor
I read with interest the article by Whittaker et al. I completely agree that the MRC scale is unsuitable for detecting the small changes in strength seen in a slowly progressive disease such as myotonic dystrophy (MD). However, I also wonder what strength a hand-held dynamometers measure. MD is a disease that affects limb muscles in the distal especially in hand muscles. Hand-held dynamometers may...
In a recent, impressive article, Teruhiko Sekiguchi et al. (1) hypothesize that misfolded proteins accumulating in some neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), can cause aggregation of their native counterparts through a mechanism similar to the infectious prion protein's induction of a pathogenic conformation onto its normal cellular isoform....
In 2002, we reported in this journal a patient with corticosteroid- responsive oculopharyngeal myopathy and an absence of chondroitin sulfate in muscle biopsies [1]. In recent years, the patient was found to have antibodies against muscle-specific kinase (MuSK). This female patient presented in 1993 at the age of 42 years with proximal muscle weakness in the neck and difficulty in swallowing, followed by blepharoptosis an...
Dear Editor
We thank Dr Derakhshan for his comments [1] regarding our report.[2]
Dr Derakhshan discusses the hypothesis that all movements are initiated from the major hemisphere,[3] which may be closely related to handedness. In neural right handers, the command of movement may originate in the left hemisphere. In cases of left hand movement, the command originated from the dominant hemisphere is once tran...
Dear Editor,
The two objectives of the study conducted by Schmidt et al.(1) were to test: A) the feasibility of multimodal imaging in Alzheimer’s disease (AD); and B) the effects of memantine in AD. We were unclear as to why the two objectives were not studied separately. Testing the feasibility of multimodal imaging procedures may be clinically valuable. However, we did not understand why it was necessary t...
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