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EDITORIALS: Rajendra Kale Neurodegenerative disorders BMJ 2001; 323: 879-880 [Full text]

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The war against neurodegenerative diseases initiates with the clinical diagnosis.

Sergio Stagnaro   (19 October 2001)

Looking forward for a historic issue, or: Is there anything besides amyloid ?

Alexei R Koudinov, Natalia V Koudinova   (19 October 2001)

Charcot Marie Tooth is neurodegenerative

Gretchen Glick   (23 October 2001)

The discourtesy of acronyms

C O Lister   (12 November 2001)

The war against neurodegenerative diseases initiates with the clinical diagnosis. 19 October 2001
Sergio Stagnaro, Specialist in Blood, Gastrointestinal and Metabolic Diseases. Riva Trigoso (Genoa) Italy Send response to journal: Re: The war against neurodegenerative diseases initiates with the clinical diagnosis.	Sirs, I agree with R Kale (1) who wrote that “tackling the problems posed by the neurodegenerative disorders is difficult. We could draw inspiration from the former US president (R. Reagan) who survived falls from horses, cancer of the skin and colon, and a bullet in the chest and is now quietly battling Alzheimer's”. However, even in such neurodegenerative disorders, in my opinion, we must aim to the early “clinical” diagnosis, possibly soon thereafter disease on-set. The diagnosis must be necessarily “clinical”, because GPs, who at first visit these patients, have to recognize the initial stage, characterized by modification of Neuronal and Cerebral Evoked Potentials, nowadays assessed bed-side by means of Biophysical Semeiotics (See: Cerebral Tumour, in htt://digilander.iol.it/semeioticabiofisica). As I have written earlier in a Rapid Response on bmj.com (16 June 2001), during an early biophysical-semeiotic research (2, 3), briefly referred in the site: http://utenti.tripod.it/la_piazzetta/professione/professione.htm.; title: “Diagnosi Semeiotico-biofisica Precoce della Malattia di Alzheimer”, I gathered interesting data, due to the fact that there is notoriously an association between high serum cholesterol, raised blood pressure and, finally, hyperinsulinism. Briefly, in healthy, from the microcirculatory point of view, during stress test both vasomotility (chaotic-deterministic oscillations of arterioles) and vasomotility (chaotic-deterministic fluctuations of nutritional capillaries and post-capillary venules) particularly in hippocampus, pre-frontal and parietal cerebral regions are maximally activated. (2, 3, 4, 5). On the contrary, in individuals with a family history positive for Alzheimer’s disease and, of course, in patients in the first stages, under identical conditions appears a particular form of microcirculatory activation, characterized by increased vasomotility and decreased vasomotion (I termed it dissociated type). In a few words, the flow- and flux-motion in the cerebral microcirculatory bed appears to be clearly decreased, due to the dangerous phenomenon of the so -called “microcirculatory blood-flow centralization”. Unfortunately, it is generally admitted that diagnosing Alzheimer’s disease, particularly in initial stages, is very difficult. In my 44-year-long clinical experience the test of acute pick of insulin secretion (2, 3) proved to be reliable in bed-side recognizing this (and other numerous) disorder, even in its first stage. Although insulin isn’t necessary in the glucose utilizations of cerebral neurons, surely in both cerebral cortex and hippocampus there is a largely amounts of insulin receptors (6). In initial stages of the disease has been demonstrated a scarse glucose metabolism in cerebral tissue: venous glucose level appears to be slightly decreased (6). The authors, in addition, demonstrated that O2 consumption is unchanged, due to the fact that the neurons utilize other “endocellular” substances rather than glucose, probably causing neurons death (7). Although insulin isn’t necessary in glucose utilizations of cerebral neurons, however in both cerebral cortex and hippocampus there is surely a largely amounts of insulin receptors (6). In addition, in the initial sages of the disease has been demonstrated a scarse glucose metabolism in cerebral tissue: venous glucose level appears to be slightly decreased (6). These authors, moreover, demonstrated that O2 consumption is unchanged, due to the fact that the neurons utilize other “endocellular” substances rather than glucose, probably causing neurons death. In summary, in the complex and non completely understood pathophysiology of Alzheimer’s disease does exist a fault response of cerebral insulin receptors, while the hormon acts likily as a growth factor. From these work hypothesis, in a previous clinical research I observed that acute pick of insulin secretion (2, 3, 4) in healthy activates the microcirculation in all biological systems, while in patients at “real” risk of Alzheimer’s disease and, naturally, in patients involved by the disease, even in early stage, microcirculatory activation is totally absent. Importantly as well as interestingly, in no other cerebral disorders, including cerebral arteriosclerosis, I did observe the absence of insulin-receptors response, i.e. the absense of microcirculatory activation, type I, associated. For the above-referred reasons, I am waiting for all papers which will be published on BMJ, 15 January 2002, devoted to neurodegenerative diseases. Yours, Stagnaro Sergio MD., Member NYAS and AAAS 1) Kale R. Neurodegenerative disorders. BMJ 2001;323:879-880 ( 20 October ). 2) Stagnaro S., Valutazione percusso-ascoltatoria della microcircolazione cerebrale globale e regionale. Atti, XII Congr. Naz. Soc. It. di Microangiologia e Microcircolazione. 13-15 Ottobre, Salerno, e Acta Med.Medit. 145, 163 1986. 3) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: la manovra di Ferrero- Marigo nella diagnosi clinica della iperinsulinemia- insulinoresistenza. Acta Med. Medit. 13, 125 1997. 4 Stagnaro S., Stagnaro-Neri M., Valutazione percusso- ascoltatoria degli attacchi ischemici transitori e della insufficienza cerebrovascolare cronica in pazienti trattati con mesoglicano. Atti, IX Congr. Naz. It. Patologia Vascolare. Copanello, 6-9 Gennaio 1987. A cura di R. Del Guercio, G. Leonardo e G. Zanini. Pg. 765, Monduzzi Ed. Bologna 1987. 5) Stagnaro S., Stagnaro-Neri M., Il Test dell’Apnea nella Valutazione della Microcircolazione cerebrale in Cefalalgici. Atti, Congr. Naz. Soc. Ita. Microangiologia e Microcircolazione. A cura di C. Allegra. Pg. 457, Roma 10-13 Settembre 1987. Monduzzi Ed. Bologna 1987 6) Hoyer S. Models of Alzheimer’s disease: cellular and molecular aspects. Journal of Neurotrasmission.(Suppl.) 49, 11, 1997. 7) Baringai M. Is Apoptosis Key in Alzheimer’s Disease? Science. 281, 1301, 28 August 1998
Looking forward for a historic issue, or: Is there anything besides amyloid ? 19 October 2001
Alexei R Koudinov, senior research scientist Assaf Harofeh Med Ctr, Dept. of Neurology; Weizmann Inst., Dept. Biol. Regul., Rehovot 76100, Israel, Natalia V Koudinova Send response to journal: Re: Looking forward for a historic issue, or: Is there anything besides amyloid ?	We were glad about today electronic call from BMJ ( 1 ) and were very happy to discover that BMJ established theme issue on neurodegenerative disorders ( BMJ October 20, 2001; 323: 879 ). We are sure that the highest standard of BMJ biomedical publishing together with the BMJ pioneering electronic publishing and open (and hopefully unbiased) peer review ( 2 ) will yield the forum (and not just journal issue) that will shape the future concepts of neurodegeneration understanding. We have to admit that the philosophy of amyloid deposition in brain of Alzheimer’s patients is a dogma that often does not need to be referenced in a scientific article. This is what everyone is (or seems) convinced about and sets as a background issue in any Alzheimer’s-related experimentation. We hope that the BMJ theme issue will provide the sounding board for different novel fascinating mechanisms of neurodegeneration and will encourage the need of concentrating efforts on other fronts of Alzheimer’s battle in addition to yet failed to bring AD cure 15-years-long amyloid odyssey. References: 1. BMJ electronic alert service 2. Koudinov AR. Pioneering new era of biomedical science publishing. BMJ published online 8 October 2001 3. Authors' Internet Office
Charcot Marie Tooth is neurodegenerative 23 October 2001
Gretchen Glick, Founder - CMTUS USA Send response to journal: Re: Charcot Marie Tooth is neurodegenerative	I would like to see a 'theme issue' centered on neurodegenerative diseases and include Charcot Marie Tooth Disease. There is a new book entitled "Rehabilitation Management in Charcot Marie Tooth Disease", by Dr. Paolo Vinci, who himself has CMT and writes with eloquence, straitforward dialogue and accompanies graphs and photos. The uniqueness of his literary accomplishs stands alone, BUT even more importantly stands to help PATIENTS with CMT show unknowing medical professionals exactly the neurodegeneratation that is involved in Charcot Marie Tooth disease and what can be done to correct and arrest the progression. How rare one finds a Doctor working in the neurodegenerative field who also has had the disease himself from childhood. Contact liliwigg@svy.com or p.vinci@libero.it for further information and please consider a special theme issue on neurodegenerative diseases and include the current hope on Charcot Marie Tooth Disease. Sincerely, G. Glick/CMTUS
The discourtesy of acronyms 12 November 2001
C O Lister, Retired Send response to journal: Re: The discourtesy of acronyms	Without prior reference or explanation this otherwise interesting article talks about "CAG repeats", but what is CAG. Acronyms are doubtless here to stay, and every profession will have a host of acronyms that are peculiar to that profesion or to specialists within that profession. Writers should ask themselves whether all their anticipated readers will be familiar with acronyms that they intend to use, for to invite people to read what they will not be able to fully understand is, in my view, discourteous, even if unintentionally so.