The excellent review shows the limits of the descriptive epidemiology in the understanding of the pathogenesis of the amyotrophic lateral sclerosis. The destruction of neurons in its classical form takes place primarily in the motor tracts which would suggest a synaptic neuron to
neuron transfer of the harmful factor thus saving initially other networks.
The excellent review shows the limits of the descriptive epidemiology in the understanding of the pathogenesis of the amyotrophic lateral sclerosis. The destruction of neurons in its classical form takes place primarily in the motor tracts which would suggest a synaptic neuron to
neuron transfer of the harmful factor thus saving initially other networks.
The hypothetical effect could be related to a special protein species found in the myelin fraction isolated from brain of an ALS patient (1). Similar protein species have also been found in two further patients.
Investigation post mortem of the brain with modern neuroscientific methods could thus advance the understanding in the causation and progress of the disease.
Professor Heikki Savolainen
References
1. Palo J, Savolainen H, Kivalo E. Comparison between the proteins of human brain myelin in subacute sclerosing panencephalitis, amyotrophic lateral sclerosis and malignant diseases. J neurol Sci 1973; 18: 175-181
In our recent letter entitled “Pisa syndrome after unilateral pallidotomy in Parkinson’s disease: an unrecognised, delayed adverse event?” (J Neurol Neurosurg Psychiatr 2007;78:329-330), we described three
Parkinson’s disease (PD) patients who developed a lean to the opposite side several years after a unilateral pallidotomy. We wondered whether this was purely disease-related or perhaps a delayed cons...
In our recent letter entitled “Pisa syndrome after unilateral pallidotomy in Parkinson’s disease: an unrecognised, delayed adverse event?” (J Neurol Neurosurg Psychiatr 2007;78:329-330), we described three
Parkinson’s disease (PD) patients who developed a lean to the opposite side several years after a unilateral pallidotomy. We wondered whether this was purely disease-related or perhaps a delayed consequence of the
pallidotomy.
We would like to correct the statement that “… postoperative imaging in these three patients confirmed that the lesions were confined to the medial pallidum (…)”. Upon further subsequent expert review of the
postoperative MRI scans, it became apparent that although the medial pallidum was indeed successfully lesioned in all three patients, in each of them the lesion was in fact more extensive. In patient 1, the surgical lesion extended into the external globus pallidus and putamen; in patient
2 into the internal capsule; and in patient 3 into the external globus pallidus, with lesions further rostrally into the area of the sella media. Nevertheless, the key issue of whether the Pisa syndrome in these patients
was related solely to their advanced stage PD or to the surgical lesion in the medial pallidum (and beyond) remains unsettled. Therefore, our invitation to report on the very long-term follow-up of pallidotomy patients in relation to the localisation of the surgical lesion still
stands.
We apologise to the readership for this unfortunate and unintended error.
Bart PC van de Warrenburg, MD, PhD
Department of Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Kailash P. Bhatia, MD & Niall P. Quinn, MD
Sobell Department of Motor Neuroscience and Movement Disorders, Institute
of Neurology, London, United Kingdom
In a patient with high-grade internal carotid artery (ICA) stenosis and frequent migraine aura-like symptoms, Dreier et al [1] demonstrated widely scattered focal laminar cortical infarcts and resolution of visual symptoms following corrective surgery. These authors carry forward the speculation that brain ischemia-related cortical spreading depression (CSD) underlies the associated visual phenomena....
In a patient with high-grade internal carotid artery (ICA) stenosis and frequent migraine aura-like symptoms, Dreier et al [1] demonstrated widely scattered focal laminar cortical infarcts and resolution of visual symptoms following corrective surgery. These authors carry forward the speculation that brain ischemia-related cortical spreading depression (CSD) underlies the associated visual phenomena.
Key areas of concern include: (i) Dissociation between headache and visual phenomenon. While CSD has been assumed as the brain aberration that underlies migraine, the factual basis for an etiological role in scintillating scotoma sine headache is even more uncertain [2,3]. (ii)
The importance of precise delineation between binocular and monocular as well as between displaceable and non-displaceable visual phenomena cannot be overemphasized [2, 3]. In the index case, scintillating scotoma in the
“right visual field” [1] cannot be translated to a monocular or uniocular, a binocular, or a homonymous defect. The clinical opportunity to test for such key ophthalmological features presents only uncommonly and must be fully explored in future. Even in patients with background neuro-ophthalmologic knowledge, unless the laterality and the displaceability of scintillating scotomata are formally determined, we will get no closer to the truth [2]. (iii) There is a distinct need to conceptually segregate the visual and non-visual neurological phenomena in this case. While the lateralizing negative neurological features (right sided-facial paresis and global aphasia) can be acceptably linked to left cortical brain ischemia, the “right-sided” scintillating scotoma merits further analysis.
(iv) Rarity of lateralizing visual scintillating phenomenon in the relatively much more common aberration of cerebral ischemia is another red flag. (v) High-frequency scintillating scotomatous attacks in this patient
(up to 10 attacks/day) [1] in the absence of associated lateralizing negative neurological deficits (possibly barring the first episode) make an ischemic etiology further unlikely. If cerebral ischemia did provoke
recurrent CSDs, why should associated negative neurological features not also be manifest? (vi) High-frequency occurrence of CSD in humans with complete recovery of neuronal function on each occasion in an ischemic field is another assumption that creeps into the equation. (vii) The fundamental nature of CSD in cerebral ischemia – adaptive or pathogenetic – has not yet been resolved [2,3]. Recording of CSD in human brain [4]
does not prove the biological nature of the phenomenon. (viii) Prevention of migraine and aborting of migraine aura with drugs that do not cross the blood-brain barrier or significantly influence cortical neuronal function
is a pharmacotherapeutic absolute that rallies against CSD-based pathophysiological algorithms [2, 3]. (ix) Occurrence of scintillating scotomata in some patients with migraine with aura after onset of headache is a clinical absolute that also challenges currently prevalent theories. (x) Contrary to the assertion in the discussion [1], lateralizing laminar cortical infarcts relevant to the scintillating scotomata have not been seen in this patient. (xi) The possibility of aggravation of pre-existing energy depletion in the cortex [1], while theoretically intriguing, is unlikely in the absence of a lateralizing lesion as well the repetitive nature of the scintillating scotoma. With 95% left ICA stenosis, each wave of CSD would further lower the available cortical energy with little likelihood of repletion sufficient to initiate the next phase/flurry of scintillating scotomata. (xii) Propagation of CSD across cerebrovascular arterial territories [1] has no experimental or theoretical basis and is a highly speculative proposal. Overall, there is a real possibility of perpetuating circular arguments and the only definitive way forward is a careful clinical neuro-ophthalmological assessment as and when such
opportunity presents. Neuro-imaging, howsoever sophisticated, will not settle such key pathophysiological issues in migraine-related phenomenology [5].
Spreading depression is known to involve the retina [2, 3] and has been suggested as a possible mechanism for scintillating scotoma related to ICA dissection [6]. Following 95% left ICA stenosis, augmented flow in
the right ICA is distinctly possible and might have set the stage for ophthalmic artery flow-related spreading depression in the right eye in this patient.
As a possible disease mechanism, the concept of CSD has guided our thinking as a default pathophysiological process over the last five decades. As scientists, however, we are obliged to dispassionately search
for gaps in our comprehension.
Vinod K Gupta
References
1. Klingebiel R, Friedman A, Shelef I, Dreier JP. Clearance of a status aurae migraenalis in response to thrombendarterectomy in a patient with high grade internal carotid artery stenosis. J Neurol Neurosurg Psychiatry 2008;79:89-90.
2. Gupta VK. Monocular and "binocular" scintillating scotomata in migraine: a semantic and theoretical paradox. CMAJ (23 November 2006). Available at: http://www.cmaj.ca/cgi/eletters/173/12/1441#6490.
3. Gupta VK. Migrainous scintillating scotoma and headache is ocular in origin: a new hypothesis. Med Hypotheses 2006;66: 454-460.
4. Dreier JP, Woitzik J, Fabricius M, et al. Delayed ischaemic neurological deficits after subarachnoid haemorrhage are associated with clusters of spreading depolarizations. Brain 2006;129: 3224–37.
This is an interesting issue about post-traumatic epilepsy (PTE) in brain injured (TBI) patients (1). The authors use spectral electroencephalography (EEG), and brain Magnetic Resonance Image study (bMRI) with contrast (Gadolinium -DTPA) using semi-quantitative technique to define the abnormal signals, and found that MRI but not EEG is more
useful to reveal the abnormal cortical signals and can predi...
This is an interesting issue about post-traumatic epilepsy (PTE) in brain injured (TBI) patients (1). The authors use spectral electroencephalography (EEG), and brain Magnetic Resonance Image study (bMRI) with contrast (Gadolinium -DTPA) using semi-quantitative technique to define the abnormal signals, and found that MRI but not EEG is more
useful to reveal the abnormal cortical signals and can predict the occurrences of PTE with statistical difference (P=0.02). Authors conclude the disruption of blood-brain barrier (BBB) plays an important role in the happening of brain swelling (increasing cortex volume), no matter in focal or generalized lesion (2).
We know the probability of seizure attacks in TBI, but usually hard to predict who will occur or who should use medications from clinical practice (3). Although the practical parameter indicated that antiepileptic drugs (AEDs) for preventive therapy in TBI is evidence-based
(4), the strategy in using preventive AEDs is different from neurologists and neurosurgeons in many countries. In Taiwan, the AEDs are given depending on the timing of TBI. If imaging study did not reveal abnormal findings (subdural hematoma, subarachnoid hemorrhage, gyri effacement, brain swelling, etc), or if PTE occurred within 2 wks even EEG revealed slow waves or cortical instability, no lasting AEDs are advised by neurologists. However, the initial preventive therapy is still advocated
by neurosurgeons in many considerations including paramedical argument.
This dilemma in using AEDs based on clinical symptoms and EEG findings are frequently debating in the combined conferences.
Another issue about the BBB permeability in TBI is high in PTE (76.9%) than in non-PTE (33.3%) patients. The presumed explanation about the disruption of BBB in this study merely based on the increasing cerebral cortex volume and slow waves activity seemed too simple (5).
Since BBB played a role in controlling certain substances into the brain tissues, its damage in TBI can be reflected by the dysregulation of cerebral blood flow (CBF)(6). The mean velocity and resistance revealed the compliance of CBF throughout the conducting arteries can partly
reflect the integrity of BBB (7). By the role of vasodilatation-vasoconstriction cascade, if BBB is intact, the constant CBF and regulatory vasoconstriction will make intra-cerebral blood volume decrease(may decrease swollen cortex volume), and also lower intracranial pressure
(ICP) effectively in using mannitol infusion (8). If BBB was breakdown, poor vascular compliance would occur by virtue of rising CBF, inconstant cerebral flow pattern, and poor effect in lowering ICP. These viewpoints
have been verified by Muzzilaar et al, in experimental and empirical studies (9).
This simple study emphasize that, in empirical view, neither conventional EEG nor clinical symptom and history taking is enough to determine the occurrence of PTE and the usage of AEDs. An additional MRI can be helpful to decide the leakage of BBB and the lasting use of medication for controlling PTE with varied presentations of seizures, headache, or cognitive impairment. The perspectives including economic burden, severity of TBI, CBF, and ICP are warranted to make this creative finding of speculated mechanism more clear in the future.
Kao-Chang Lin, Jinn-Rung Guo
References
1. Annegers JF, Hauser WA, Coan SP, et al. A population-based study of seizures after traumatic brain injuries. N Engl J Med. 1998; 338:20-24.
2. Tomkins O, Shelef I, Kaizerman I, et al. Blood-Brain Barrier Disruption in Post-Traumatic Epilepsy. JNNP. 2007. (Ahead online published).
3. Garga N and Lowenstein DH. Posttraumatic epilepsy: a major problem in desperate need of major advances. Epilepsy Curr. 2006; 6:1-5.
4. Bernard S, Chang and Daniel H, Lowenstein. Practice parameter: Antiepileptic drug prophylaxis in severe traumatic brain injury: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2003; 60:10-16.
5. Rosner MJ, Coley IT: Cerebral perfusion pressure: A hemodynamic mechanism of mannitol and the postmannitol hemogram. Neurosurgery 1987; 21: 147-156.
6. Visocchi M, Chiaretti A, Cabezas D, et al. Hypoflow and hyperflow in diffuse axonal injury. Prognostic and therapeutic Implications of transcranial doppler sonography evaluation. Journal of Neurosurgical
sciences 2002; 46: 10-17.
7. Newell DW, Aaslid R, Stoos R, et al. The relationship of blood flow velocity fluctuations to intracranial pressure B waves. J Neurosurgery1992; 76: 415-421.
8. Bradley J. Phillips, Tisha K. et al. Traumatic Brain Injury: A Review. The Internet Journal of Surgery. 2005. Volume 6.
9. Muizelaar JP, Lutz HA III, Becker DP. Effect of mannitol on ICP and CBF and correlation with pressure auto-regulation in severely head-injured patients. J Neurosurgery 1984; 61: 700-706.
Dear Editor
The excellent review shows the limits of the descriptive epidemiology in the understanding of the pathogenesis of the amyotrophic lateral sclerosis. The destruction of neurons in its classical form takes place primarily in the motor tracts which would suggest a synaptic neuron to neuron transfer of the harmful factor thus saving initially other networks.
The hypothetical effect could be relat...
Dear Editor
In our recent letter entitled “Pisa syndrome after unilateral pallidotomy in Parkinson’s disease: an unrecognised, delayed adverse event?” (J Neurol Neurosurg Psychiatr 2007;78:329-330), we described three Parkinson’s disease (PD) patients who developed a lean to the opposite side several years after a unilateral pallidotomy. We wondered whether this was purely disease-related or perhaps a delayed cons...
Dear Editor
In a patient with high-grade internal carotid artery (ICA) stenosis and frequent migraine aura-like symptoms, Dreier et al [1] demonstrated widely scattered focal laminar cortical infarcts and resolution of visual symptoms following corrective surgery. These authors carry forward the speculation that brain ischemia-related cortical spreading depression (CSD) underlies the associated visual phenomena....
Dear Editor
This is an interesting issue about post-traumatic epilepsy (PTE) in brain injured (TBI) patients (1). The authors use spectral electroencephalography (EEG), and brain Magnetic Resonance Image study (bMRI) with contrast (Gadolinium -DTPA) using semi-quantitative technique to define the abnormal signals, and found that MRI but not EEG is more useful to reveal the abnormal cortical signals and can predi...
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