We read with great interest the review by Grossman on neurologic
complications of celiac disease in a recent issue of Pract Neurol.(1)
Using an evidence-based approach, the author has carefully and critically
analyzed articles published in the last decade on the most common
neurologic manifestations associated with celiac disease, namely ataxia,
epilepsy, and peripheral neur...
We read with great interest the review by Grossman on neurologic
complications of celiac disease in a recent issue of Pract Neurol.(1)
Using an evidence-based approach, the author has carefully and critically
analyzed articles published in the last decade on the most common
neurologic manifestations associated with celiac disease, namely ataxia,
epilepsy, and peripheral neuropathy.
Grossman has rigorously dissected the evidence for, and against, the
possible association of celiac disease with neurological manifestations.
The association, the review concludes, does not seem to hold up when
referral bias is considered or when strict criteria are applied.
While still leaving open the possibility of an association between celiac
disease and certain neurologic disorders, the author calls for well-
controlled and prospective studies to help clarify the issue.
We would like to call attention to a 2-year prospective study, which was
recently published.(2)
After a retrospective study of a cohort of celiac children, where we did
not find a correlation between neurologic manifestations and improvement
on gluten-free diet (3), we undertook a prospective study in an adult
celiac population in order to evaluate the incidence of neurologic
symptoms and examine the response to gluten-free diet.
Our prospective study enrolled 71 patients with histologically proven
celiac disease, who were prospectively followed for up to 28 months.
Of the 71 patients, 69 were consecutively referred to our centre from the
university’s gastroenterology department, whereas 2 directly sought
treatment at our clinic for neuropathic symptoms. Forty-two patients were
on gluten-free diet at recruitment. Adherence to the diet was assessed by
testing for anti-transglutaminase antibodies. All patients underwent
neurological and electrophysiological evaluation at recruitment and at
every follow-up visit.
The results of the prospective study showed that 3 patients were affected
by sensory-motor polyneuropathy. However, 2 of the 3 patients with
polyneuropathy had sought treatment at our clinic for neuropathic
symptoms. Considering this referral bias, only one of the 69 celiac
patients referred for evaluation was affected by neuropathy. Several other
manifestations affecting the nervous system were detected in our celiac
population (4 with headache, 4 with depression, 4 with entrapment
syndromes, 1 with facial hemispasm, and one of the 3 patients with
neuropathy was also affected by epilepsy). However, the relatively common
occurrence in the general population of headache, depression, and
entrapment neuropathies makes it difficult to conclude a likely
association with celiac disease.
Antibody reactivity to neural antigens was detected in 30/71 (42.2%)
patients, but there was no clear correlation between anti-neural
reactivity and active neurologic dysfunction.
Follow-up of 62 patients during gluten-free diet did not reveal
significant changes in electrophysiology. However, in 2 patients with
neuropathy, improvement in symptoms did correlate with the diet.
In conclusion, the results of our prospective study do not seem to support
a causal relationship between biopsy-proven celiac disease and neurologic
disease in the studied group of patients.
We agree with Grossman that further well-controlled studies are warranted
in order to clarify the relationship, as well as the effect of diet.
The use of proper outcome measures should be considered when evaluating
therapeutic efficacy of any intervention (e.g. diet) in such a
heterogeneous disease.(4)
While further research may end up refuting an association between celiac
disease and neurologic dysfunction, gluten sensitivity, as defined only on
the basis of presence of anti-gluten antibodies, might prove to have a
connection with certain neurologic and psychiatric deficits.(5)
The potential relevance and significance of elevated levels of these
antibodies in the absence of celiac disease deserve proper attention as
well and should not be overlooked.
References
1. Grossman G. Neurological complications of coeliac disease: what is
the evidence?
Pract Neurol. 2008;8:77-89.
2. Briani C, Zara G, Alaedini A, Grassivaro F, Ruggero S, Toffanin
E, Albergoni MP, Luca M, Giometto B, Ermani M, De Lazzari F, D’Odorico A,
Battistin L. Neurological complications of celiac disease and autoimmune
mechanisms: a prospective study.
J Neurommunol. 2008;195(1-2):171-5.
3. Briani C, Ruggero S, Zara G, Toffanin E, Ermani M, Betterle C,
Guariso G. Anti-ganglioside antibodies in children with celiac disease: correlation
with gluten-free diet and neurological complications.
Alimentary
Pharmacology and Therapeutics, 2004;20:231-235.
4. Hobart JC, Cano SJ, Zajicek JP, Thompson AJ. Rating scales as
outcome measures for clinical trials in neurology: problems, solutions,
and recommendations.
Lancet Neurol. 2007;6:1094-105.
5. Briani C, Samario D, Alaedini A. Celiac disease: from gluten to
autoimmunity.
Autoimmun Rev. 2008;7(8):644-50.
I wish to commend the authors for their paper on functional vitamin
B12 deficiency.
It is important that despite the array of investigative tools that may be
available at the disposal of clinicians, clinical signs and symptoms are
given their due emphasis particularly in Vitamin B12 deficiency. The
authors report a case where the serum cobalamin was normal in the face of
anaemia and neurol...
I wish to commend the authors for their paper on functional vitamin
B12 deficiency.
It is important that despite the array of investigative tools that may be
available at the disposal of clinicians, clinical signs and symptoms are
given their due emphasis particularly in Vitamin B12 deficiency. The
authors report a case where the serum cobalamin was normal in the face of
anaemia and neurological damage, at the other end of the spectrum are
cases with normal haemoglobin levels but with significant morbidity. A
recent report by Rajkumar AP and Jebaraj P (1) was of a non anaemic
patient with psychosis who returned to complete self care following
treatment with Vitamin B12.
The diagnostic value of properly elicited clinical signs and symptoms
cannot be overemphasized.
Reference
1. Chronic Psychosis associated with Vitamin B12 deficiency.
J Assoc
Physicians India 2008 Feb; 56: 115-6
I read with interest the important case report of Turner and Talbot
describing clinical subacute combined degeneration in a patient with
“functional” vitamin B12 deficiency (defined by elevated levels of the B12
-dependent metabolites, methylmalonic acid and homocysteine, despite
normal serum B12 values).1 It is important to note that although their
patient did not improve with hydroxycobalamin the...
I read with interest the important case report of Turner and Talbot
describing clinical subacute combined degeneration in a patient with
“functional” vitamin B12 deficiency (defined by elevated levels of the B12
-dependent metabolites, methylmalonic acid and homocysteine, despite
normal serum B12 values).1 It is important to note that although their
patient did not improve with hydroxycobalamin therapy, progression of her
disease was halted. This pattern is consistent with B12 deficiency since
neurologic changes become irreversible if B12 therapy is delayed for more
than 6 months.2
Importantly, functional vitamin B12 deficiency may be far more
prevalent than classic B12 deficiency where serum vitamin B12 levels are
clearly depressed.3 Moreover, recent reports suggest that vitamin B12
therapy can indeed improve neuropathy in some patients with functional B12
deficiency as well as in some patients with normal B12, methylmalonic acid
and homocysteine values.3-5 Finally, B12, methylmalonic acid and
homocysteine values have been shown to fluctuate widely in untreated
individuals.3 Thus, when the clinical picture is consistent with B12
deficiency, therapeutic trials of B12 should be considered regardless of
the results of B12 and metabolite testing.
2. Chanarin I. The Megaloblastic Anaemias, 2nd Edition, Oxford, UK.
Blackwell Scientific Publications, 1979:287-290.
3. Solomon LR. Cobalamin-responsive disorders in the ambulatory care
setting” unreliability of cobalamin, methylmalonic acid and homocysteine
testing.
Blood 2005; 105:978-985.
4. Solomon LR. Disorders of cobalamin (vitamin B12) metabolism:
emerging concepts in pathophysiology, diagnosis and treatment.
Blood
Reviews 2007; 21:113-130.
5. Nardin RA, Amick ANH, Raynor EM. Vitamin B12 and methylmalonic acid
levels in patients presenting with polyneuropathy.
Muscle Nerve 2007;
36:532-535.
Richard Hughes does not include leprosy in his list of peripheral
nerve disorders.(1) While it is true that new cases of leprosy are
declining rapidly , as a result of effective anti-bacterial therapy, there
are still frequent numbers with residual disabilities in endemic
countries.
In neurological text books, a mononeuropathy or multiple
mononeuropathy is regarded as the sole neurolog...
Richard Hughes does not include leprosy in his list of peripheral
nerve disorders.(1) While it is true that new cases of leprosy are
declining rapidly , as a result of effective anti-bacterial therapy, there
are still frequent numbers with residual disabilities in endemic
countries.
In neurological text books, a mononeuropathy or multiple
mononeuropathy is regarded as the sole neurological lesion in leprosy. In
1923, Monrad-Krohn described a sensory polyneuropathy involving
superficial sensory modalities in patients with leprosy.(2) A similar
pattern of sensory loss was found in a group of northern Nigerian leprosy
patients, without prior knowledge of Monrad-Krohn’s observations.(3)
There are still no references to Monrad-Krohn’s findings in neurological
text books. This omission is serious because a patient with this sensory
polyneuropathy can develop trophic ulcers, mutilation of the extremities
and Charcot’s joints. Moreover, this polyneuropathy, because of the
distribution of the sensory loss, cannot be caused by direct invasion of
the peripheral nerves by Mycobacterium leprae
Sensory loss in leprosy can be acute in onset with simultaneous
involvement of all four limbs(3) and could be an autoimmune response to an
antigen in sensory peripheral nerve rather than a direct response to
M.leprae . In order to test this hypothesis, rabbits were injected with a
homogenate of human sensory peripheral nerve plus adjuvant and
electrophysiological recordings were made from the hind limb. It was found
there was a diminished amplitude in the slower component of C fibres but
the conduction velocity and amplitude of A delta fibres were normal.(4) An
animal model of diabetic neuropathy could be developed as a result of
these experiments.(5) Some of the rabbits previously injected with sensory
nerve developed a state of granulomatous hypersensitivity. ie. Skin
testing in sensitised rabbits results in the formation of a granuloma,(6)
with invasion of mononuclear cells into the endoneurium of dermal nerves,
together with axonal damage.(7) The antigen involved is a non-myelin
membrane fraction.(8) A similar antigen in the central nervous system
could be used to induce tolerance, which if successful could lead to a
vaccine against multiple sclerosis.(9)
The observations on the clinical aspects of leprosy may therefore
lead to a greater understanding of the pathogenesis of diabetic neuropathy
and multiple sclerosis, in which case it will reinforce the maxim that
there is no substitute for precise clinical examination, with no need for
auxiliary aids, apart from a pin and a piece of cotton wool.
7. Crawford CL, Hardwicke PMD. Somatic unmyelinated degeneration in
rabbits with granulomatous hypersensitivity produced by a non-myelin
antigen sensory peripheral nerve.
Acta Neuropath 1979; 45: 1-7.
8. Hardwicke PMD, Crawford CL. Nature of the antigen of human sensory
nerve that induces granulomatous hypersensitivity.
J Neurochem 1978; 30:
1609-1611.
9. Crawford CL. Is it possible to induce oral tolerance using a non-myelin
peripheral nerve antigen?
Available at
http://www.jci.org/eletters/view/32132 Accessed 22 January 2009.
It is not correct that the Democratic Party has historically been the
major underwriter of biomedical research in the USA. American science,
and biomedical science in particular, benefited historically from
substantial bipartisan support. The major increase in NIH funding of the
Clinton period owed at least as much to actions of moderate Republicans
like Rep. John Porter (Republican of Illinois) an...
It is not correct that the Democratic Party has historically been the
major underwriter of biomedical research in the USA. American science,
and biomedical science in particular, benefited historically from
substantial bipartisan support. The major increase in NIH funding of the
Clinton period owed at least as much to actions of moderate Republicans
like Rep. John Porter (Republican of Illinois) and Sen. Arlen Spector
(Republican of Pennsylvania) as it did to the Clinton administration. The
predominance of the hard right in the Republican Party, with its
marginalization of Republican moderates, and the anti-intellectualism of
the Bush administration had a deplorable effect on federal funding of
science. Bush administration science funding policies, however, are not
the historic norm of the Republican Party.
I write as a fervent Obama supporter and very, very left of center
Democrat - but fair is fair.
The admission that a neurologist has stopped examining patients(1) is
a disturbing one, given the fact that "the practice of medicine is the
art of drawing conclusions from incomplete evidence"(2), thanks to the
fact that, as clinicians, "we work in a probabilisic enviroment in which
the evidence we gather bears an imperfect relationship to its cause"(3).
The admission that a neurologist has stopped examining patients(1) is
a disturbing one, given the fact that "the practice of medicine is the
art of drawing conclusions from incomplete evidence"(2), thanks to the
fact that, as clinicians, "we work in a probabilisic enviroment in which
the evidence we gather bears an imperfect relationship to its cause"(3).
Accordingly, the evidence initially gathered from history taking has to
undergo subsequent "fine tuning" through the medium of clinical
examination, special investigations, and, in some intances, also through
the medium of the literature search. We omit any of the stages of that
work up to our peril, given the fact that "the dominant cause of error in
the faulty data-gathering category [lies] in the subcategory of
ineffective, incomplete, or faulty work up", exemplified by a missed
diagnosis of subdural hematoma in a patient seen after a car accident
because "the physical examination was incomplete"(4). A potential benefit
of clinical examination is that it might reduce the risk of "premature
closure" whereby the clinician fails to consider other possibilities once
an intitial diagnosis has been reached(4). With the benefit of clinical
examination, even a clinician who is guilty of premature closure can learn
from the experience of recognising that "I didn't reassess the situation
when things didn't fit"(5). Clinical examination also helps to cut down on
the number of "blunderbuss" investigations,thereby releasing scarce
resources such as computerised tomography(CT) and magnetic resonance
imaging(MRI) for use in patients who are too old and frail to cooperate
with meticulous and long-drawn out clinical examination.
These are the
patients who "miss out" in the era of high-tech medicine. On the one
hand,after presenting with atypical symptoms, they do not receive the
benefit of even a cursory clinical examination. To compound diagnostic
error, their atypical symptoms are then falsely attributed to old age,
and, as a consequence, they are also denied the benefit of the high-tech
investigations that are themselves supposed to be a short cut to
diagnosis.
I read the title of Dr. Hawkes’ editorial three times before I was
certain I had read it correctly1. As a fourth year medical student about
to apply for a neurology residency, I was initially bewildered. When I
read on though, I was impressed not only with his candidness, but also by
the validity of what he was saying; although I am a newcomer, it does not
take long to appreciate that imaging is cent...
I read the title of Dr. Hawkes’ editorial three times before I was
certain I had read it correctly1. As a fourth year medical student about
to apply for a neurology residency, I was initially bewildered. When I
read on though, I was impressed not only with his candidness, but also by
the validity of what he was saying; although I am a newcomer, it does not
take long to appreciate that imaging is central to current diagnosis of
neurological disorders. However, from the perspective of someone about to
commence her career, I would like to make a plea to save the neurological
examination.
Neurology traditionally has been a field which medical students find
intimidating. Full of esoteric names, bizarre pathologies and a lengthy
examination the significance of which is often unclear to us at our stage
of training. As we go through our rotation, some like me are captivated by
the complexity and organization of this supercomputer, when many of its
secrets and pathologies are revealed after acquiring the necessary
examination skills. The exam further provides us with an opportunity to
feel like a true physician because it helps seal the doctor patient
relationship, providing the healing touch if I may say.
Lastly, we find
the neurological exam quirky and fun to practice on each other.
Finally I do have a more pragmatic argument. After decades of
experience, it makes sense that Dr. Hawkes feels confident diagnosing and
treating certain patients without a formal exam. However, he himself notes
that "the ability to take a history and examine simultaneously is a
technique that takes a few years to acquire". This level of mastery is
indeed something to strive for, but in the meantime it would be hugely
irresponsible of me to neglect a thorough examination of my patients. And
if those with such expertise as Dr. Hawkes sit back and let things change,
how will the next generation of neurologists ever acquire the skill set
necessary to practice the art of neurology?
Perhaps because I don't have Dr. Hawkes' degree of experience (I have
approximately 25 years of practice experience), I disagree very strongly
with his conclusion. Careful examination remains the cornerstone of
neurologic practice. I agree that a great deal of information is gleaned
from informal examination - watching the patient walk into the exam room,
etc. I agree as well that for paroxysmal d...
Perhaps because I don't have Dr. Hawkes' degree of experience (I have
approximately 25 years of practice experience), I disagree very strongly
with his conclusion. Careful examination remains the cornerstone of
neurologic practice. I agree that a great deal of information is gleaned
from informal examination - watching the patient walk into the exam room,
etc. I agree as well that for paroxysmal disorders - migraine, epilepsy,
TIAs, etc. - history is the most important aspect of the evaluation. But
efficient and careful examination is indispensable. Lets look at one of
the examples cited by Dr. Hawkes. No younger patient, for example, with
typical migraine features should undergo imaging unless they have an
examination abnormality. Deferring to patient wishes is a pallid excuse
and leads to waste of tax dollars (this is true in the US and UK).
Indeed, imaging of all headache patients will result in identification of
a significant number of unrelated and largely benign findings, additional
imaging studies, and heightened patient anxiety. Polite discussion and
deflection of patient requests for inappropriate imaging is better care.
At a time when we are likely to see increased emphasis on clinical
evaluation and decision making, it would be an enormous mistake for
neurologists to permit erosion of reliance on the powerful and distinctive
method of clinical examination.
I read with interest the editorial by Dr. Hawkes titled “I have
stopped examining patients!”1. The title appropriately has an exclamation
mark at the end highlighting his shocking claim. I have to commend Dr.
Hawkes for finally coming out and admitting boldly and maybe somewhat
proudly what most neurologists already know but are afraid to accept.
Bedside clinical neurology is a dyin...
I read with interest the editorial by Dr. Hawkes titled “I have
stopped examining patients!”1. The title appropriately has an exclamation
mark at the end highlighting his shocking claim. I have to commend Dr.
Hawkes for finally coming out and admitting boldly and maybe somewhat
proudly what most neurologists already know but are afraid to accept.
Bedside clinical neurology is a dying art and I admit many times in the
office I have been guilty of a cursory neurological examination. A brief
flash of the pen light into the patient’s eyes, a tap with the reflex
hammer here and there, stand up, walk and voila I am done. The founding
fathers of our great art would surely be turning in their graves if they
saw a modern neurologist like me at work today.
But should we just sit back and let things change? Dr. Hawkes says
yes and why not? It is for the best after all. Why swim against the tide?
I have a slightly different view. I still remember what made me choose
neurology from among the various disciplines of medicine. The thrill of
watching the big toe go up in a patient with a hemispheric stroke, the eye
signs in a patient with multiple sclerosis and the first time I saw facial
myokymia. My joy and fascination with neurology was unparalleled and
remains to this day. James Parkinson in his short monograph on shaking
palsy in 1817 described six patients in total. Parkinson was an astute
observer, and his report contained observations from three patients he saw
in his clinic and three individuals he observed on city streets. Much of
the description of the longitudinal course of the illness was derived from
his observations of a single case only. Till today the diagnosis of
Parkinson’s disease remains a clinical diagnosis. One made after taking a
history and examining the patient for the three cardinal signs namely
resting tremor, rigidity and bradykinesia. None of the advanced
neuroimaging capabilities at my disposal can improve my ability to
diagnose this and many other neurological conditions.
I am sure that Dr. Hawkes shall agree with me that the "joy" and
"fun" of neurology lies in the examination. For that reason in itself we
all should strive to save this dying art.
Dear Editor,
We read with great interest the review by Grossman on neurologic complications of celiac disease in a recent issue of Pract Neurol.(1)
Using an evidence-based approach, the author has carefully and critically analyzed articles published in the last decade on the most common neurologic manifestations associated with celiac disease, namely ataxia, epilepsy, and peripheral neur...
Dear Editor,
I wish to commend the authors for their paper on functional vitamin B12 deficiency.
It is important that despite the array of investigative tools that may be available at the disposal of clinicians, clinical signs and symptoms are given their due emphasis particularly in Vitamin B12 deficiency. The authors report a case where the serum cobalamin was normal in the face of anaemia and neurol...
Dear Editor,
I read with interest the important case report of Turner and Talbot describing clinical subacute combined degeneration in a patient with “functional” vitamin B12 deficiency (defined by elevated levels of the B12 -dependent metabolites, methylmalonic acid and homocysteine, despite normal serum B12 values).1 It is important to note that although their patient did not improve with hydroxycobalamin the...
Dear Editor,
Richard Hughes does not include leprosy in his list of peripheral nerve disorders.(1) While it is true that new cases of leprosy are declining rapidly , as a result of effective anti-bacterial therapy, there are still frequent numbers with residual disabilities in endemic countries.
In neurological text books, a mononeuropathy or multiple mononeuropathy is regarded as the sole neurolog...
Dear Editor,
It is not correct that the Democratic Party has historically been the major underwriter of biomedical research in the USA. American science, and biomedical science in particular, benefited historically from substantial bipartisan support. The major increase in NIH funding of the Clinton period owed at least as much to actions of moderate Republicans like Rep. John Porter (Republican of Illinois) an...
Dear Editor,
The admission that a neurologist has stopped examining patients(1) is a disturbing one, given the fact that "the practice of medicine is the art of drawing conclusions from incomplete evidence"(2), thanks to the fact that, as clinicians, "we work in a probabilisic enviroment in which the evidence we gather bears an imperfect relationship to its cause"(3).
Accordingly, the evidence initial...
Dear Editor,
I read the title of Dr. Hawkes’ editorial three times before I was certain I had read it correctly1. As a fourth year medical student about to apply for a neurology residency, I was initially bewildered. When I read on though, I was impressed not only with his candidness, but also by the validity of what he was saying; although I am a newcomer, it does not take long to appreciate that imaging is cent...
Dear Editor,
Perhaps because I don't have Dr. Hawkes' degree of experience (I have approximately 25 years of practice experience), I disagree very strongly with his conclusion. Careful examination remains the cornerstone of neurologic practice. I agree that a great deal of information is gleaned from informal examination - watching the patient walk into the exam room, etc. I agree as well that for paroxysmal d...
Dear Editor,
I read with interest the editorial by Dr. Hawkes titled “I have stopped examining patients!”1. The title appropriately has an exclamation mark at the end highlighting his shocking claim. I have to commend Dr. Hawkes for finally coming out and admitting boldly and maybe somewhat proudly what most neurologists already know but are afraid to accept.
Bedside clinical neurology is a dyin...
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