Professor Wardlaw has crafted an inspiring critique on the clinico-
pathological spectrum of lacunar stroke that is a delight to read.[1] In
elucidating the pathophysiology of lacunar stroke, it is, however,
particularly difficult to break out of our mindset that is moulded on the
pattern of the ischemic stroke model, particularly given the concurrence
of small cortical infarcts with the lacunar syndr...
Professor Wardlaw has crafted an inspiring critique on the clinico-
pathological spectrum of lacunar stroke that is a delight to read.[1] In
elucidating the pathophysiology of lacunar stroke, it is, however,
particularly difficult to break out of our mindset that is moulded on the
pattern of the ischemic stroke model, particularly given the concurrence
of small cortical infarcts with the lacunar syndrome. The strength of this
editorial lies in the conceptualization of a difference between the
uncommon (10-15%) embolic/middle cerebral artery stenotic lacunar stroke
and the common non-embolic/stenotic lacunes. Nevertheless, certain areas
of this synthesis are open to discussion; what is left out is also
sometimes more important than what finds inclusion in an analysis.
To exclude a role for hypertension or diabetes mellitus in lacunar
strokes on the ground that there is not a striking difference in the
incidences of these two major risk factors between lacunar and non-lacunar
infarctions [1] appears to be a rather premature conclusion stimulated by
the quest for a distinctive pathophysiology for lacunar infarctions. While
underscoring appropriately the particular predisposition of certain
patients to suffer repeated lacunar infarctions as well as the apparent
link to clinically significant white matter hyperintensities or lesions
(WML) in the elucidation of a "small cerebral arteriolar" pathology,
Wardlaw has missed the critical difference between the genesis of the
ischaemic stroke and WML.[2] WML are found in hypertensive encephalopathy,
puerperal eclampsia, migraine, and therapy with cyclosporine, interferon-
á, and tacrolimus.[2] Also, a characteristic difference prevails in the
distribution of posterior circulation territory cortical infarcts and deep
WML in migraine patients.[2] Prolonged, diffuse hyperperfusion prevails in
the cerebral cortex, thalamus and basal ganglia in migraine.[3] Vasogenic
cerebral oedema resulting from intense but-self limited cerebral
hyperperfusion probably underlies WML in hypertensive encephalopathy and
migraine.[2] This proposal raises an important issue: why does profound
cerebral hyperperfusion in hypertensive encephalopathy or migraine spare
the cortical arteriolar network relatively?
A crucial anatomic difference exists between deep lenticular
arterioles embedded in brain tissue and more superficial cortical
arterioles. In states of sudden profound cerebral hyperperfusion,
lenticular arterioles with limited distensibility are likely to be more
susceptible to rheological barotraumas and undergo segmental arteriolar
wall disorganization (lipohyalinosis or fibrinoid necrosis). Such a
pressure distortion of deeper arterioles is far more likely to be "around"
rather than at the "end" of the abnormal segment, as has also been
speculated.[1] Vasospasm,[1] nevertheless, is quite unlikely to contribute
to WML or lacunar infarcts or to "leaks" with extravasation of plasma
proteins or red blood cells (micro-haemorrhages). Secondly, in seeking a
mechanism for endothelial failure, we must ask why prolonged diabetes
mellitus cannot affect pressure-sensitive walls of the lenticular
arterioles as it does the retinal arterioles. Finally, the perfusion of
the periventricular region where WML are predominantly seen is
particularly and inversely susceptible to variations of the brain
cerebrospinal fluid (CSF) pressure. Sudden lowering of CSF pressure can
induce episodic lenticular arteriolar dilatation and vasogenic oedema.
A diffuse cerebral arteriolar pathological vascular anomaly, as
suggested,[1] is unlikely to underlie lacunar infarcts. The suddenness of
the lacunar infarct also questions the operation of a presumed gradual
pathological process [1] diffusely affecting cerebral arterioles.
Unpredictable progression of lacunar stroke symptoms or asymptomatic
additional lacunar infarcts further militates against an orderly
pathophysiological process.
We stand at the threshold of a paradigm shift in thinking about
lacunar strokes and WML.
References
1. Wardlaw JM. What causes lacunar stroke? J Neurol Neurosurg
Psychiatry 2005;76:617-9.
2. Gupta VK. White matter hyperintensities: pearls and pitfalls in
interpretation of MRI abnormalities. Stroke 2004 35: 2756-7; published
online before print November 4 2004,
doi:10.1161/01.STR.0000147158.89251.5b.
3. Kobari M, Meyer JS, Ichijo M, Imai A, Oravez WT. Hyperperfusion of
cerebral cortex, thalamus and basal ganglia during spontaneously occurring
migraine headaches. Headache 1989;29:282-9.
Nemoto et al. reported that jitter was abnormal in 93%
of seropositive patients but only in 46% of seronegative
patients. This finding is quite different from our previous
reports.[1-2] Our study showed that abnormality in the
SFEMG was almost equal on both groups, being 91%
in seropositive and 92% in seronegative groups.[2]
However, clearly all of parameters in SFEMG were
worse in seropositive gro...
Nemoto et al. reported that jitter was abnormal in 93%
of seropositive patients but only in 46% of seronegative
patients. This finding is quite different from our previous
reports.[1-2] Our study showed that abnormality in the
SFEMG was almost equal on both groups, being 91%
in seropositive and 92% in seronegative groups.[2]
However, clearly all of parameters in SFEMG were
worse in seropositive group as noted by Nemoto et al.
However, there was no significant statistical difference
between two groups in all parameters. Thus, SFEMG
has been extremely helpful in diagnosis of
seronegative MG when the repetitive nerve stimulation
(RNS) test is negative. I wonder whether the stimulation
SFEMG technique, the diagnostic criteria of MG or the
small number of patients made the difference. The only
significant difference we have observed between two
groups was the rate of abnormality in the RNS test:
65.8% in seronegative group versus 83.3% in
seropositive group. Similar findings were found by
Nemoto et al. though their abnormality rate is much
lower.
References
1. Oh SJ, Kim DE, Kuruoglu R, Bradley RJ, Dwyer D.
Diagnostic sensitivity of the laboratory tests in
myasthenia gravis. Muscle Nerve 1992;15:720-724
2.Oh SJ. Electrophysiological characteristics in
seronegative myasthenia gravis. Annals of the New
York Academy of Sciences 1993;681:584-587.
Anatomical textbook in humans shows us that 11th cranial nerve
originates from lower medulla to C5/6 anterior cell column, innervating
the trapezius (caudal column) and sternocleidomastoideus muscle (rostral
column). There also exist anterior cell columns innervating the cervical
muscles. Platysma muscles are innervated by both the facial nucleus and
high cervical cord in mammals. Our patient also h...
Anatomical textbook in humans shows us that 11th cranial nerve
originates from lower medulla to C5/6 anterior cell column, innervating
the trapezius (caudal column) and sternocleidomastoideus muscle (rostral
column). There also exist anterior cell columns innervating the cervical
muscles. Platysma muscles are innervated by both the facial nucleus and
high cervical cord in mammals. Our patient also had right trapezius
weakness, therefore we agree that the platysma could be innervated by the
11th cranial nerve as well. Spinal trigeminal nucleus exists in up to C2/3
in humans. However, in our patient with C3 intramedullary lesion we did
not see Dejerine's onion-peel sensory loss, Bell's cruciate paresis or
respiratory dysfunction.
We appreciate your interesting comment, thank you.
We read with interest the report by Kuoppamäki et al. on their case of
a
young man with bilateral globus pallidus lesions and signs of
parkinsonism [1]. We have recently come across a patient with similar
clinical and MRI findings following a single head trauma. We propose that
lesion in this brain region regardless of causes can produce features of
parkinsonism.
We read with interest the report by Kuoppamäki et al. on their case of
a
young man with bilateral globus pallidus lesions and signs of
parkinsonism [1]. We have recently come across a patient with similar
clinical and MRI findings following a single head trauma. We propose that
lesion in this brain region regardless of causes can produce features of
parkinsonism.
Five years ago, this 60 year-old man sustained a closed head injury
when
assaulted. He was unconscious for 24 hours before making a slow
recovery.
Features of parkinsonism include mild hypomimia, generalised
bradykinesia, asymmetric cogwheel rigidity and intermittent rest tremor
of the right leg. He had a mild shuffling gait and impaired postural
recovery reflexes.
MRI scan showed hypointensity in both basal ganglia on T2 axial image (Figure 1), corresponding to haemosiderin deposition. This is consistent
with the patient’s CT brain 5 years ago which showed bilateral basal
ganglia haemorrhage, a small right frontal subdural haematoma, and an
undisplaced fracture of right frontal cranium.
Figure 1. Hypointensity in both basal ganglia on T2 axial image.
There are a few reported cases of post-traumatic parkinsonism
following
a single head injury, usually severe, associated with substantia nigra
and/or basal ganglia lesions [2,3]. This case provides further
neuroimaging evidence of post-traumatic parkinsonism following a
single head trauma.
References
1. Kuoppamäki. M., et al. Parkinsonism following bilateral lesions
of the
globus pallidus: performance on a variety of motor tasks shows
similarities with Parkinson’s disease. J Neurol Neurosurg Psychiatry,
2005. 76: p. 482-90.
2. Doder, M., et al., Parkinson's syndrome after closed head injury:
a
single case report. J Neurol Neurosurg Psychiatry, 1999. 66(3): p. 380-5.
3. Bhatt, M., et al., Posttraumatic akinetic-rigid syndrome
resembling
Parkinson's disease: a report on three patients. Mov Disord, 2000. 15(2):
p. 313-7.
If the platysma is innervated from the high spinal cord, I think this will
be through the XI cranial nerve; in this case there should be also
weakness of shoulder elevation.
I wonder about the sensory loss in the onion or Dejerine pattern,
particularly close to the forehead, ear, and chin areas as it may result
from lesion to caudal spinal tract of the V and about the respiratory
function. Als...
If the platysma is innervated from the high spinal cord, I think this will
be through the XI cranial nerve; in this case there should be also
weakness of shoulder elevation.
I wonder about the sensory loss in the onion or Dejerine pattern,
particularly close to the forehead, ear, and chin areas as it may result
from lesion to caudal spinal tract of the V and about the respiratory
function. Also if weakness is major in the upper extremities than in the
lower as described in central cord syndrome and cruciate paralysis.
Is EMG study of Platysma useful in some way here?
Regarding the article by van Vliet et al. [1] reporting the results of an outcome study comparing two 'approaches' to physiotherapy following stroke:
The authors make a common error in assuming that an
outcome study provides evidence of effectiveness of an
intervention. It does not, as Herbert [2] has recently
pointed out - "outcome measures measure outcome. They do not measure the effects...
Regarding the article by van Vliet et al. [1] reporting the results of an outcome study comparing two 'approaches' to physiotherapy following stroke:
The authors make a common error in assuming that an
outcome study provides evidence of effectiveness of an
intervention. It does not, as Herbert [2] has recently
pointed out - "outcome measures measure outcome. They do not measure the effects of intervention." (p.3). The
authors have misrepresented their findings by
concluding "our results indicate that physiotherapists
may choose to use either BB or MSB treatment as
neither was found to be more effective than the other".
This is poor advice to clinicians, in particular because,
without a control group, the authors present no
evidence that either treatment was effective - their
results could illustrate a natural improvement occurring
over time.
Overall the results were actually very poor,
given that there was virtually no change on Rivermead
Motor Assessment, Motor Assessment Scale and 6m
walk after one month. If we take gait speed as an
example, none of the subjects were walking at a speed
considered fast enough for community competency
(1.1-1.5m/s). The dismal results of the 6m walk test (at
6mths: 0.76 and 0.64m/s), shown to over-estimate
walking speed [3], surely reflect the
ineffectiveness of the gait rehabilitation given during
this study. The authors also suggest that dose and
timing might be more important than treatment given,
another unwarranted conclusion- providing more of
something that is not effective is not a good idea. Dose
and timing, however, are probably critical.
The study has a number of flaws that could have
affected the results, not all of which are acknowledged
in discussion of the limitations:
- The two groups of patients were treated by
physiotherapists in the same hospital environment (in
the same ward).
- Physiotherapists treating both groups are likely to
have come from a similar professional educational
background, which would have involved extensive
experience of Bobath therapy. Those treating the
'movement science-based' group received some
training from one of the authors.
- No indication is given that treatment was
standardised in any way and details of treatments
themselves were not reported in the paper. The
therapists used written guidelines but these are not
provided. It is reported, however, that guidelines for
each patient were prepared by the treating therapist.
This could suggest that each patient had different
treatment. The reader is referred to an earlier paper for
information about treatment given [4] but this does not make the details any clearer.
However, the descriptions, given by the 'trained
observers', of treatment actually given make it clear that
in neither group was treatment based on the sources
cited and that the methods used were identical,
different only in degree. We have some interest in this
as early publications of ours are listed as source
material. The only treatment method recognisable to us
from our publications is 'feedback'. There is no
reference to task-oriented or strength training, to
applied biomechanics, to the need for intensive
practice in groups and independently, or for the use of
multiple repetitions in order to increase strength and
control in the limbs- factors that are generally thought of
as "movement science based".
- The patients overall received very little treatment - a
median time of 23mins (IQR 13-32mins) was spent on
5 days each week. This reinforces the well documented
finding that little time is typically spent by patients in
physiotherapy treatment while in rehabilitation. Patients
received therapy for a variable number of days/weeks
for "as long as was needed"- no details were given.
- The Motor Assessment Scale is said to measure the
consequences of motor impairment. It does not - it
measures motor performance on several common
functional actions (sit-to-stand, walking etc). It was not
developed by therapists using the MSB approach- in
1985 there were few objective clinical tests that looked
at functional movement, so we developed and tested
one. This was before the suggestion that
physiotherapists should develop new interventions out
of the emerging findings from research into human
movement coming from biomechanics and
neuroscience - the so-called movement sciences.
- The paper illustrates that it is hazardous to attempt to
test "approaches" to treatment. The notion of an
approach is vague and suggests subjectivity. This is
why most studies of physiotherapy investigate specific
treatments such as strength training, treadmill training,
task-specific training, in randomised controlled trials. It
could be argued that this study really tested the
approaches of individual therapists since they
apparently wrote their own guidelines "based on their
own knowledge and experience and their interpretation
of the literature". Since the therapists probably came
from a similar professional background and worked in
the same place it would not be surprising if they were
found to give similar treatments. There is also little
point in testing "whole treatment approaches" in order
to "study the interaction of different treatment elements",
as the authors suggest, if those elements themselves
are not effective. Several recent randomised controlled
investigations have shown that certain specific and
standardised treatments are effective when studied in
isolation and that therapy programs incorporating those
specific treatments can also be effective.
This is a very poor contribution to rehabilitation
literature and it is disappointing to see it published in
2005. The Bobath approach has soldiered on for over 5
decades, with the name preserved regardless of what
individual therapists are actually doing. It is a flaw in the
delivery of therapy services that therapists are free to do
what they like in clinical practice. It is not unrealistic to
expect that they keep to a set of proscribed guidelines,
based on sound scientific knowledge and the evidence
available. The message from this paper is that
physiotherapists can continue with what they are doing.
This despite the findings that both groups improved
very little.
You might be interested that we have recently
published a new textbook for physiotherapy
undergraduates. It provides protocols and guidelines
(science - and where possible evidence-based), with
explanations about progressing dosage and with an
emphasis on organising rehabilitation so a maximum
time is spent by the patient in training and practice of
everyday tasks to reduce the emphasis one-on-one
therapy time (i.e. in groups and semi-supervised). A
major focus is on strength training and exercise to
improve cardiovascular fitness. This book in fact
addresses many of the suggestions raised by Marsden
and Greenwood in their excellent Editorial
Commentary.
With best regards
Dr RB Shepherd
Dr JH Carr
References
1. van Vliet, Lincoln and Foxall (2005). Comparison of Bobath based and movement science based treatment for stroke: a randomised controlled trial. J Neurol Neurosurg Psychiatry 2005; 76: 503-508.
2. Herbert R, Jamtvedt, Mead J et al. (2005) Editorial:
Outcome measures measure outcomes, not effects of
intervention. Aust J Physiother 51, 3-4.
3. Dean CM, Richards CL, Malouin F (2001) Walking
speed over 10m overestimates locomotor capacity after
stroke. Clin Rehabil 15, 415-421.
4. Van Vliet PM, Lincoln NB, Robinson E (2001)
Comparison of the content of two physiotherapy
approaches for stroke. Clin Rehabil 15, 398-414.
We thank J. Kwan for his interest in our article. As he mentioned, we
studied 203 patients aged 16 to 45 years using a standard protocol
including blood tests, CT and/or MRI, 12 lead electrocardiography, and
ultrasound examination of the brain supplying arteries. Additional
investigations to rule out the presence of patent foramen ovale,
vasculitis, cardiac arrhythmias, cervical artery dissections, et...
We thank J. Kwan for his interest in our article. As he mentioned, we
studied 203 patients aged 16 to 45 years using a standard protocol
including blood tests, CT and/or MRI, 12 lead electrocardiography, and
ultrasound examination of the brain supplying arteries. Additional
investigations to rule out the presence of patent foramen ovale,
vasculitis, cardiac arrhythmias, cervical artery dissections, etc., were
carried out at the discretion of the treating physician. It is our policy
to investigate just in a few selected young patients for the presence
thrombophilia, because of the lack of strong evidence supporting an
association with ischemic stroke [1,2].
The high prevalence of
thrombophilia makes the probability of a coincidental finding high [3,4].
At least 1 thrombophilic disorder is present in approximately 10% to 15%
of the white Western European population [5]. The attributable risk of
stroke for the thrombophilias is likely to be low, though, it might be of
clinical relevance for particular ethnic groups, type of thrombophilia, or
etiological subtypes of the stroke such as thromboembolism from an area of
stasis in the veins via a right-to-left shunt [6]. Given the considerable
costs of the laboratory tests to investigate for thrombophilia (several
hundreds of US $ or Euros) and the lack of therapeutic consequences (e.g.
aspirin therapy would not be replaced by anticoagulation), we believe that
there is no justification for thrombophilia screening in stroke patients.
Recent studies confirm this strategy, and only factor V Leiden and
prothrombin gene (20210 G/A) mutation may play a small role in a subtype
of stroke [7].
Further research is needed to evaluate the response of
etiologically relevant thrombophilias to different treatment regimens.
Since then, the testing for thrombophilia should be carried out on a case
by case basis, after weighting the importance of all possible etiologies.
References
1. Bushnell CD, Goldstein LB. Diagnostic testing for coagulopathies
in patients with ischemic stroke. Stroke 2000;31:3067-3078.
2. Karttunen V, Hiltunen L, Rasi V, Et al. Factor V Leiden and
prothrombin gene mutation may predispose to paradoxical embolism in
subjects with patent foramen ovale. Blood Coagul Fibrinolysis 2003;14:261-
268.
3. Hankey GJ, Eikelboom JW, van Bockxmeer FM, Lofthouse E, Staples
N, Baker RI. Inherited thrombophilia in ischemic stroke and its pathogenic
subtypes. Stroke. 2001;32:1793-1799.
4. Zunker P, Hohenstein C, Plendl HJ, Zeller JA, Caso V, Georgiadis
D, Allardt A, Deuschl G. Activated protein-C resistance and acute ischemic
stroke: relation to stroke causation and age. J Neurol 2001;248:701-704.
5. Martinelli I. Pros and cons of thrombophilia testing: pros. J
Thromb Haemost. 2003; 1: 412–413.
6. Hankey GJ, Eikelboom JW. Editorial comment--Routine thrombophilia
testing in stroke patients is unjustified. Stroke. 2003;34:1826-1827.
7. Walker ID, Greaves M, Preston FE, Et al. Investigation and
management of heritable thrombophilia. Br J Haematol 2003;114:512-528.
We are grateful to Dr. Braune for his comments regarding
our recent paper [1], and appreciate the opportunity for
further discussion. The most important thing in our paper
was that MIBG scintigraphy was carried out in the largest
number of parkinsonian patient-series to verify the
usefulness of the examination in clinical routine. Since
all of them were outpatients, only clinical diagnosis was
av...
We are grateful to Dr. Braune for his comments regarding
our recent paper [1], and appreciate the opportunity for
further discussion. The most important thing in our paper
was that MIBG scintigraphy was carried out in the largest
number of parkinsonian patient-series to verify the
usefulness of the examination in clinical routine. Since
all of them were outpatients, only clinical diagnosis was
available for our patients.
The normal lower limit of H/M ratio is important,
since it may directly influence sensitivity and specificity
for diagnosing Parkinson's disease [PD]. The cut-off level
of 1.84, obtained from 10 normal volunteers in our study,
was slightly high compared with that of 1.75 provided by
the recent meta-analysis of six MIBG studies, based on 69
normal subjects [2]. Therefore we re-calculated the
sensitivity and specificity for diagnosing PD using the cut
off of 1.75 in our patient-series to confirm our first
conclusion. Although the sensitivity (85.3%) remained
high, the specificity (40.6%) was still considerably low
despite re-calculation, suggesting that the low specificity
described in the recent publication [1] did not result from
high cut off value.
Several disorders with Lewy bodies are reportedly
related to low cardiac MIBG uptake [3-5]. Our patients with
Alzheimer's disease (AD) showed surprisingly low MIBG
uptake, conflicting with the previous observations [3-5].
Recent pathological study revealed that alpha-Synuclein
lesions, including Lewy bodies, co-existed with AD
pathology, and that these lesions were found in more than
30-40% of AD patients [6,7]. Furthermore incidental Lewy
bodies are reportedly associated with age [8]. The AD
patients in our study were characterized by one or more
motor symptoms, and were relatively older (77.0 +/- 6.5
years) than those in the previous reports [3-5].
Therefore, Lewy body pathology might exist more frequently in our AD
patients compared with those in the previous observations
[3-5], resulting in low H/M ratios. The H/M ratios in our
patients suffering from dementia with Lewy bodies (DLB)
were extremely low, consistent with the previous reports [3-5]. The diagnostic criterion for DLB in our study was
based on the probable criterion of the Consortium on DLB
[9]. The specificity of the criteria is reportedly high
while its sensitivity is low [10]. Clinically, our DLB
patients were, therefore, quite uniform, resulting in low
MIBG uptake. Reduced MIBG uptake found in our patients
with cerebrovascular disease is also interesting, although
precise causative factors for the low uptake remains
unclear. Since such patients might have several risks for
vascular events, the low uptake might result from cryptic
heart ischemia, which was not detectable using ECG, as well
as incidental Lewy body pathology related to aging.
Nothing but only post-mortem analysis can resolve these
speculations.
We believe our data probably match with the recent
pathological knowledge regarding Lewy bodies. Our
conclusion is that MIBG is useful, but not absolute, in
clinical practice.
References
1. Nagayama H, Hamamoto M, Ueda M, et al. Reliability of
MIBG myocardial scintigraphy in the diagnosis of
Parkinson's disease. J Neurol Neurosurg Psychiatry
2005;76:249-51.
2. Braune S. The role of cardiac metaiodobenzylguanidine
in
the differential diagnosis of parkinsonian syndromes. Clin
Autonom Res 2001;11:351-355.
3. Watanabe H, Ieda T, Katayama T et al. Cardiac (123)I-
meta-iodobenzylguanidine (MIBG) uptake in dementia with
Lewy bodies: comparison with Alzheimer's disease. J Neurol
Neurosurg Psychiatry 2001;70:781- 783.
4. Yoshita M, Taki J, Yamada M. A clinical role for
[(123)I]MIBG myocardial scintigraphy in the distinction
between dementia of the Alzheimer's-type and dementia with
Lewy bodies. J Neurol Neurosurg Psychiatry 2001;71:583-588.
5. Oide T, Tokuda T, Momose M, et al. Usefulness of
[123I]metaiodobenzylguanidine ([123I]MIBG) myocardial
scintigraphy in differentiating between Alzheimer's disease
and dementia with Lewy bodies. Intern Med 2003;42:686-690.
6. Mikolaenko I, Pletnikova O, Kawas CH, et al. Alpha-
synclein lesions in norlka aging, Parkinson disease, and
Alzheimer disease: Evidence from the Baltimore longitudinal
study of aging (BLSA). J Neuropahol Exp Neurol 2005;64:156-
62.
7. Arai Y, Yamazaki M, Mori O, et al. Alfa-synuclein-
positive structure in cases with sporadic AlzheimerÕs
disease: morphology and its relationship to tau
aggregation. Brain Res 2001;888:287-96.
8. Saito Y, Ruberu NN, Sawabe M, et al. Lewy body-related
alpha-synucleinopathy in aging. J Neuropathol Exp Neurol
2004;63:742-9.
9. McKeith IG, Galasko D, Kosaka K, et al. Consensus
guidelines for the clinical and pathologic diagnosis of
dementia with Lewy bodies (DLB): report of the consortium
on DLB international workshop. Neurology 1996;47:1113-24.
10. Luis CA, Barker WW, Gajaraj K, et al. Sensitivity and
specificity of three clinical criteria for dementia with
Lewy bodies in an autopsy-verified sample. Int J Geriatr
Psychiatry 1999;14:526-33.
In my earlier eLetter I wrote, "Increasing blood flow to the brain by
increasing pCO2 may do much more metabolic harm than good. Indeed in
upregulating oxidative phosphorylation and down regulating ATP-dependent
enzymatic activity... keeping the intracerebral pH abnormally low could
reduce the need for blood flow to abnormally low levels". Is this
statement compatible with the effects of high altitud...
In my earlier eLetter I wrote, "Increasing blood flow to the brain by
increasing pCO2 may do much more metabolic harm than good. Indeed in
upregulating oxidative phosphorylation and down regulating ATP-dependent
enzymatic activity... keeping the intracerebral pH abnormally low could
reduce the need for blood flow to abnormally low levels". Is this
statement compatible with the effects of high altitude on pH and
intracranial pressure? A rise in intracranial pressure caused by acute
cerebral oedema is one of the more feared complications of high altitude
afflicting climbers.
Acute ascent is accompanied 5 days later by a respiratory alkalosis
suggested to have been caused by "a fall in the chemoreflex threshold and
.. corrected by an elevation in the concentration of weakly dissociated
protein anions" [1]. Bicarbonate was not significantly changed. In another
study of blood gases a significant increase in arterial pH from 7.34 to
7.43 (p <0.01) was observed with a prolonged stay at 3500 m that
remained significantly increased at 5800 m [2]. The effective renal plasma
flow reduced significantly (p <0.01) from 615.6 at sea level (SL) to
381.5 ml x min(-1) x 1.73 m(-2) at 5800 m. Cerebral blood flow (CBF) is
also reduced at high altitude.
Chronic changes in CBF was studied by 133Xe inhalation dynamic single
photon emission computer tomography in 8 members of a climbing expedition
to the Himalayas. "With one exception they had all previously climbed at
high altitudes. All stayed above 6,500 m for approximately 3 weeks, and 5
reached the summit of Mt. Everest. One year after the completion of the
expedition the average CBF in climbers was still more than 15% lower than
in the reference group. The climbers had higher relative CBF increase
after injection of the carbonic anhydrase inhibitor acetazolamide [which
causes a metabolic acidosis] than the reference subjects" [3].
In 12 subjects, ascending from 150 to 3,475 m, CBF was 24% increased
at 24 h [45.1 to 55.9 initial slope index (ISI) units] and 4% increased at
6 days (47.1 ISI units). Increases in CBF were similar in subjects with or
without acute mountain sickness (AMS) and acetazolamide-provoked increases
of CBF in AMS subjects caused no acute change in symptoms [4]. (Presumably
this effect is short-lived and son replaced by a decline in blood flow).
In a randomized, double-blind cross-over study 10 subjects were
exposed to a simulated altitude of 4500 m for 10 h after administration of
placebo, acetozolamide (250 mg bid) or theophylline (250 mg bid). Almost
all subjects showed a decrease in inner cerebrospinal fluid (iCSF) volumes
(placebo - 10.3%, P= 0.02; acetazolamide - 13.2%, P= 0.008, theophylline -
12.2%, n.s.). There was no correlation between AMS symptoms and fluid
shift [5].
The influence of acetazolamide (ACZ) upon the ability to perform and
sustain maximal and submaximal exercise bouts under normoxic and hypoxic
conditions was examined in four groups of healthy male subjects (N = 27).
ACZ (500 mg) or inert placebo (Pla) was administered prior to exercise in
a quasi-randomized, double-blind, crossover fashion. ACZ was shown to
lower venous pH (ACZ, 7.31 +/- 0.01, vs Pla, 7.35 +/- 0.08) and
bicarbonate (ACZ, 22.4 +/- 0.27 mM, vs Pla, 25.4 +/- 0.6 mM) and to
elevate urine pH (ACZ, 7.36 +/- 0.06, vs Pla, 5.84 +/- 0.19).
No significant effect of ACZ upon VO2, VCO2, RER, or heart rate (HR)
was observed during submaximal exercise (75% of peak VO2) although VE was
increased by 14% and time to exhaustion (EXHt) was reduced by 29%. Prior
to exercise, venous pH (ACZ, 7.39 +/- 0.04, vs Pla, 7.44 +/- 0.007) and
bicarbonate were lower with ACZ (ACZ, 21.6 +/- 0.46 mM, vs Pla, 24.2 +/-
0.25 mM), while urine pH was higher (ACZ, 7.6 +/- 0.07, vs Pla, 5.9 +/-
0.25). Other than a higher PCO2 (increased ox-phos) and lower venous
lactate (decreased anaerobuc glycolysis) with ACZ, no significant
differences were identified at peak VO2 [6].
Might then the respiratory alkalosis that develops at high altitude
reduce blood flow with prolonged exposure by upregulating oxidative
phosporylation and down regulating anaerobic glycolysis, the antithesis of
the metabolic effects of acute liver failure [7]? The decline in paCO2
might have achieved this by a mass action on oxidative phosporylation [8].
What then of the benedicial effects of ACZ in AMS? Might the metabolic
acidosis it induces have a similar effect on oxidative phosporylation and
the symptomatic benefits be due to improved efficiency of ATP resynthesis?
Might then ACZ have reduced the efficiency of oxidative
phosporylation by decreasing the availability of lactate normally
generated in muscles during exercise for ATP resynthesis by oxidative
phosporyation in accordance with the lactate shuttle hypothesis [9] even
though ox;phos might have been upregulatd by hypocarbia? What then of the
cerebral oedema which may develop at high altitude?
If upregulating oxidative phoporylation decreases the need for
cerebral blood flow, as proposed in my earlier Letter, might it also
decrease intracraniail pressure by decreasing intracerebral capillary
density and hence blood volumes? If so upregulating anaerobic glycolysis
could have the opposite effects. (The acute decline in CSF might have been
a cytoprotective response to the acute and apparently transient increase
in CBF). If so the capacity for cytoprotectve responses mounted to
accommodate cellular stesses might also be compromised. Hence the reduced
time to exhaustion from exercise caused by ACZ. The critical determinants
of cerebral oedema might well be the pathologic changes that might be
induced by a critical decline in ability of the liver and other organs to
recyle anarobic metabolities from the brain and the conversion of
xanthine dehydrogenase to xanthine oxidase with accelerated free radical
release [10].
ACZ and supplmentary oxygen at high altitude delivered by face mask
might both be double edged swords benefittting climbers by increasing by
mass action both the capacity for ATP resynthesis by oxidative
phoporylation at rest and the potential for exceeding the anaerobic
threshold and generating free radicals during acute rductive stresses
such as exercise. It might be safer and more effective for climbers to
rely upon physiological acclimatiation to avoid AMS and to deliver
supplementary oxygen intraperitoneally via a chronically implanted system
should the need ever arise [11]. Viagra, which has become a popular
substitute for ACZ, might also be a double-edged sword.
The statement I made in my earlir eLetter appears to be compatible
with the effects of high altitude on pH and intracranial pressure.
References
1. Somogyi RB, Preiss D, Vesely A, Fisher JA, Duffin J. Changes in
respiratory control after 5 days at altitude.
Respir Physiol Neurobiol. 2005 Jan 15;145(1):41-52.
2. Singh MV, Salhan AK, Rawal SB, Tyagi AK, Kumar N, Verma SS,
Selvamurthy W. Blood gases, hematology, and renal blood flow during
prolonged mountain sojourns at 3500 and 5800 m.
Aviat Space Environ Med. 2003 May;74(5):533-6.
3. Rootwelt K, Stokke KT, Nyberg-Hansen R, Russell D, Dybevold S.
Reduced cerebral blood flow in high altitude climbers.
Scand J Clin Lab Invest Suppl. 1986;184:107-12.
5. Fischer R, Vollmar C, Thiere M, Born C, Leitl M, Pfluger T, Huber
RM. No evidence of cerebral oedema in severe acute mountain sickness.
Cephalalgia. 2004 Jan;24(1):66-71.
6. Stager JM, Tucker A, Cordain L, Engebretsen BJ, Brechue WF,
Matulich CC. Normoxic and acute hypoxic exercise tolerance in man
following acetazolamide.
Med Sci Sports Exerc. 1990 Apr;22(2):178-84.
7. Anaerobic glycolysis in acute liver failure
Richard G Fiddian-Green (9 March 2005) eLetter re: J G O’Grady
Acute liver failure
Postgrad Med J 2005; 81: 148-154.
8. pCO2, pH and the regulation of aerobic / anaerobic glycolysis.
Richard G Fiddian-Green (15 March 2005) eLetter re: Jerry Yee and Irawan
Susanto
Sublingual Capnometry : In Search of Its Holy Grail
Chest 2000; 118: 894-896.
9. Dienel GA, Cruz NF. Nutrition during brain activation: does cell-
to-cell lactate shuttling contribute significantly to sweet and sour food
for thought?
Neurochem Int. 2004 Jul-Aug;45(2-3):321-51.
10. Is increasing FiO2 above 0.2 always harmful?
Richard G Fiddian-Green (23 March 2005) eLetter re: K. S. Khaw, C. C.
Wang, W. D. Ngan Kee, C. P. Pang, and M. S. Rogers
Effects of high inspired oxygen fraction during elective Caesarean section
under spinal anaesthesia on maternal and fetal oxygenation and lipid
peroxidation
Br. J. Anaesth. 2002; 88: 18-23.
11. Might enteric or intraperitoneal oxygen improve performance?
Richard G Fiddian-Green
BJSM Online, 29 Jun 2004 eLetter re: G Neumayr, R Pfister, G Mitterbauer,
A Maurer, and H Hoertnagl
Effect of ultramarathon cycling on the heart rate in elite cyclists
Br J Sports Med 2004; 38: 55-59.
We read the report of Deus Silva et al. [1] with great interest. The
authors describe a patient with right ear pain, fever and diffuse
pulsatile headache, who later developed pancerebellar symptoms.
Cerebrospinal fluid (CSF) examination revealed pleocytosis (138 cells,
predominantly lymphocytes) and elevated protein. CT and MR-imaging
revealed an "unusual empty delta sign" and thrombosis of the lat...
We read the report of Deus Silva et al. [1] with great interest. The
authors describe a patient with right ear pain, fever and diffuse
pulsatile headache, who later developed pancerebellar symptoms.
Cerebrospinal fluid (CSF) examination revealed pleocytosis (138 cells,
predominantly lymphocytes) and elevated protein. CT and MR-imaging
revealed an "unusual empty delta sign" and thrombosis of the lateral part
of the left transverse sinus was diagnosed. The presumed thrombus was
hypointense on T1 and hyperintense on T2-weighted MR-images, thus
demonstrating an unusual signal behaviour.
We would like to propose an alternative diagnosis for this case; in
our opinion, the CT and MRI findings are compatible with arachnoid
granulations of the left transverse sinus. Signal behaviour of this almost
always benign anatomical variant (largely isointense with CSF on both T1
and T2 weighted images) [2] is identical with that of the presumed empty
delta sign. Furthermore, the clinical presentation of this case is not
characteristic for a thrombosis of the transverse sinus, as noted by the
authors. Same is true for the observed CSF pleocytosis, which would rather
suggest a meningeal infection.
2. Roche J, Warner D: Arachnoid granulations in the transverse and
sigmoid sinuses: CT, MR, and MR angiographic appearance of a normal
anatomic variation. AJNR Am J Neuroradiol. 1996;17(4):677-683
Dear Editor,
Professor Wardlaw has crafted an inspiring critique on the clinico- pathological spectrum of lacunar stroke that is a delight to read.[1] In elucidating the pathophysiology of lacunar stroke, it is, however, particularly difficult to break out of our mindset that is moulded on the pattern of the ischemic stroke model, particularly given the concurrence of small cortical infarcts with the lacunar syndr...
Dear Editor,
Nemoto et al. reported that jitter was abnormal in 93% of seropositive patients but only in 46% of seronegative patients. This finding is quite different from our previous reports.[1-2] Our study showed that abnormality in the SFEMG was almost equal on both groups, being 91% in seropositive and 92% in seronegative groups.[2] However, clearly all of parameters in SFEMG were worse in seropositive gro...
Dear Editor,
Anatomical textbook in humans shows us that 11th cranial nerve originates from lower medulla to C5/6 anterior cell column, innervating the trapezius (caudal column) and sternocleidomastoideus muscle (rostral column). There also exist anterior cell columns innervating the cervical muscles. Platysma muscles are innervated by both the facial nucleus and high cervical cord in mammals. Our patient also h...
Dear Editor,
We read with interest the report by Kuoppamäki et al. on their case of a young man with bilateral globus pallidus lesions and signs of parkinsonism [1]. We have recently come across a patient with similar clinical and MRI findings following a single head trauma. We propose that lesion in this brain region regardless of causes can produce features of parkinsonism.
Five years ago, this 60...
Dear Editor,
If the platysma is innervated from the high spinal cord, I think this will be through the XI cranial nerve; in this case there should be also weakness of shoulder elevation.
I wonder about the sensory loss in the onion or Dejerine pattern, particularly close to the forehead, ear, and chin areas as it may result from lesion to caudal spinal tract of the V and about the respiratory function. Als...
Dear Editors,
Regarding the article by van Vliet et al. [1] reporting the results of an outcome study comparing two 'approaches' to physiotherapy following stroke:
The authors make a common error in assuming that an outcome study provides evidence of effectiveness of an intervention. It does not, as Herbert [2] has recently pointed out - "outcome measures measure outcome. They do not measure the effects...
Dear Editor,
We thank J. Kwan for his interest in our article. As he mentioned, we studied 203 patients aged 16 to 45 years using a standard protocol including blood tests, CT and/or MRI, 12 lead electrocardiography, and ultrasound examination of the brain supplying arteries. Additional investigations to rule out the presence of patent foramen ovale, vasculitis, cardiac arrhythmias, cervical artery dissections, et...
Dear Editor,
We are grateful to Dr. Braune for his comments regarding our recent paper [1], and appreciate the opportunity for further discussion. The most important thing in our paper was that MIBG scintigraphy was carried out in the largest number of parkinsonian patient-series to verify the usefulness of the examination in clinical routine. Since all of them were outpatients, only clinical diagnosis was av...
Dear Editor,
In my earlier eLetter I wrote, "Increasing blood flow to the brain by increasing pCO2 may do much more metabolic harm than good. Indeed in upregulating oxidative phosphorylation and down regulating ATP-dependent enzymatic activity... keeping the intracerebral pH abnormally low could reduce the need for blood flow to abnormally low levels". Is this statement compatible with the effects of high altitud...
Dear Editor,
We read the report of Deus Silva et al. [1] with great interest. The authors describe a patient with right ear pain, fever and diffuse pulsatile headache, who later developed pancerebellar symptoms. Cerebrospinal fluid (CSF) examination revealed pleocytosis (138 cells, predominantly lymphocytes) and elevated protein. CT and MR-imaging revealed an "unusual empty delta sign" and thrombosis of the lat...
Pages