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PD AND HORMONES PART TWO OF FIVE
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Date:         Tue, 19 Sep 1995 01:21:23 +1000
From:         Lloyd Stewart <[log in to unmask]>
Subject:      diamox
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To John Cottingham

Here is some info about diamox / acetazolamide, no controlled trial becoz no
funding and the idea seems too radical, and I am not well enough, but see the
paper by Factor which made it to Medline. Forgive the translation of Ramos
paper. My own comments reflect my early enthusiasm and speculation.

Diamox is not a sugar pill so check the package insert if you are tempted.
Angel Ramos argues for a buildup of lactate which follows if mitochondria are
not working properly, but this occurs in the brain and has only recently been
measrable.

---------------------------------------------
Acetazolamide in a Case of Parkinson's Disease
Case Report
---------------------------------------------

The following is extracted from the patients own excellent written account.
The author discussed the case in person with the patient, her daughter and her
ophthalmologist.

TAS1, an active postmenopausal grandmother, developed PD in 1984. In 1987 she
was prescribed ACZ 250 mg twice daily after a corneal graft. She continued
disipal TDS.  Her PD improved, despite missed disipal tablets. By Dec. 1988
she was taking L- Dopa/Carbidopa (L/C) 100/25 TDS. The ACZ was ceased and 'the
Parkinson's symptoms came back, in particular the rigidity of the (L) arm
plus tremor returned and ..(she)... was quite depressed.....so .. commenced it
again....after a short time ...was feeling well again with no sign of a
tremor'.

Sept 1990 ....'left off ACZ for 6 weeks and ...becoming less able to
cope, losing weight.'She was too unwell to visit her neurologist. She
restarted ACZ and was 'well again in two or three months.' She regained the
lost weight. (1) She is stable on three L/C and  ACZ 375 mg per day. She
continues 'The effects of ACZ take up to 28 days to wear off...its effect on
some symptoms is slow when commencing,..  the aches and stiffness of the arm
(are) almost immediately relieved.' 'ACZ does not replace L-dopa ..' (She
tried ACZ without L-dopa) She uses less L-dopa with more flexibility.

Discussion

No improvement was expected by the patient, her medical advisors not being
aware of reported benefits of ACZ including less L-dopa; less tremor, aching,
seborrhea, weight loss and constipation; fewer fluctuations, slower
progression and better quality of life. (1)

Two  drug withdrawals support causation. She titrated dose, observed onset
times, offset times, and L-dopa synergy. She established a window effect.  She
made excellent handwritten notes.

She inspired others to try ACZ. LRS improved in tremor, lethargy, writing,
driving and control. NZ1 developed postural hypotension, (60 mm systolic), but
his tremor improved.

Treatment of Parkinson's disease (PD) with acetazolamide (ACZ) was reported
by Ramos (1,2) Stewart, Cuthbert and Whealing, (3) and Factor (4).

Ramos supplements ACZ with partial rebreathing. He titrated dose below 125 mg
per day in 8 cases. (5)

ACZ and ammonium chloride cause metabolic acidosis, which hyperpolarises
neurones and stimulates respiration. ACZ points to an hypoxic contribution to
PD, and to prevention of some cases of PD by avoiding recurrent hypoxia, a
potent source of free radicals.

The  diaphragm is not immune to stiffness, rigidity, poverty of movement and
hyperkinesias. Respiratory control, mitochondria, and Kreb's cycle enzymes have
been implicated in PD. (3). Neurones need ATP to make neurotransmitters. The
proposed actions of ACZ are independent of neurotransmitter type, consistent
with ACZ use in essential tremor, epilepsy,(4), Alzheirmer's Disease and
Huntingdon's Chorea. (5) ACZ is used in macular oedema (CME) at 125 mg/day. (6)
The mechanism may be the same.

Raising pH by hyperventilation leads to neuromuscular hyperexcitability.
These principles explain the paresthesiae, Chvostek's and Trousseau's signs
of anxiety attacks, and the treatment of neuromuscular hyperexcitability by
rebreathing or ACZ to raise carbon dioxide and lower pH.

Neuronal hyperexcitability arises from hypocalcemia, calcium channel blockers,
hypoparathyroidism, alkalosis, neurotransmitter deficiency or excess,
insufficient ATP to drive ion pumps, and hyperventilation. Increasing [H+]
causes a stabilising hyperpolarisation, Es, proportional to [H+]. Es =k[H+]
Low pH stimulates respiration and cerebral bloodflow.

Respiratory stimulants such as theobromine, progesterone, and ammonium chloride
may improve PD (1,3) Hyperbaric oxygen is possibly therapeutic. (7) Obstructive
hypoxia, (strangulation), anemic hypoxia, (CO), and histotoxic hypoxia (CO via
Cytochrome C), cause PD.(3)

PD and CME are reported to improve when diuretics such as thiazides, which
cause alkalosis and hypoxia, are ceased. (1,8) Hypoxic theory predicts the
association of hypoxic free radical damage, Down syndrome, sleep apnea, PD and
Alzheimer's disease. (9,10,11)

A trial of ACZ 125 mg/day, ACZ 125mg/day plus partial rebreathing, partial
rebreathing, and placebo, is worthwhile.

Beware of complications of ACZ including allergic, bone marrow, renal,
electrolyte, and acid-base problems.

Acknowledgments: The author wishes to thank Joyce Carey, Cynthia Carey, Eddie
Ross and Marjory Cuthbert.

Lloyd R Stewart FRACS
7 Hogan Street
Box 608
Wangara tta Victoria 3676
Australia


References
1.Ramos, Angel M. Enfermadad de Parkinson. Ciclo alcalosis metabolica
-acidosis metabolica - alcalosis respiratoria. La Prensa Medica Argentina
1986; 73:303-307
2.Ramos, Angel M. Enfermadad de Alzheimer. Enfermadad de Parkinson. Ciclo
alcalosis metabolica - acidosis metabolica - (acidosis lactica) -alcalosis
respiratoria. Orientation therapeutica La Prensa Medica Argentina 1987;
74:313-317
3.Stewart LR, Cuthbert M, Whealing D. Parkinson's disease, hypoxia, lethargy,
acetazolamide (diamox), hypoventilation, mitochondria and mountain
climbing.In: Conference Papers of the second Australian national
multidisciplinary conference on Parkinson's disease. Brisbane: Parkinson's
Syndrome Society of Queensland, Box 521 Lutwyche Queensland.  1993; 108-127
4.Factor SA. Acetazolamide therapy of menstrual-related fluctuations in
Parkinson's disease. Movement Disorders 1993;8:240-241
5.Ramos Angel M. Central nervous system. Atrophic degenerative syndrome.
Metabolic alkalosis - metabolic acidosis (lactic acidosis) - respiratory
alkalosis cycle. English draft. Buenos Aires: Angel Ramos Nunez 3649,
5to.Piso, Dpto.B 1430 Capital Federal Buenos Aires Rep Argentina.
6.Gelisken O, Gelisken F, Ozcetin H, Treatment of chronic macular oedema with
low dose acetazolamide. Bull Soc Belge Ophthal 1990; 238: 153-160
7.Neretin VYa, Lobov MA, Kotov SV,Cheskidova GF, Molchanova GS, Safronova OG.
hyperbaric oxygenation in comprehensive treatment of Parkinsonism. Neurosci.
Behav. Physiol. 1990; 6:490-492
8.Stewart, LR. Sleep apnea precedes mild Parkinson's disease by two decades.
Poster Presentation, Annual Scientific Congress, Royal Aust. College of
Ophthalmologists, Hobart,1993. Unpublished.
9.Brown, P. Rescuing minds from disease and decay. New Scientist 1992; 14 Nov:
2-7
10.Marcus CL, Keens TG, Bautista DB, von Pechman WS, Ward SL. Obstructive
sleep apnea in children with Down syndrome. Pediatrics 1991;88 1:132-139.
11.Vieregge P, Ziemans G, Freudenbererg M, Pionski A, Muysers A, Schulze B.
Extrapyramidal features in Down's syndrome: clinical evaluation and family
history. J. Neurol. Neurosurg. Psychiatry. 1991 1 34-38.
12.Da Costa JL. Chronic hypoventilation due to diminished sensitivity of the
respiratory centre assosciated with Parkinsonism. Med. J. Aust, 1972, 1:
373-376.

---------------------------------------------
Appendix 1 Paper by Angel Ramos
---------------------------------------------

Author: Ramos, Angel  Nunez 3649 -p.5o - "B"  Cod. 1430 -
                Buenos Aires Argentina Phone 542 5267

Title:          Parkinson's Disease. Cycle Metabolic Alkalosis
                Metabolic Acidosis Respiratory Alkalosis.
                Treatment with Acetazolamide Prensa Med. Argent.,73: 303, 1986

Abstract:

The study of the arterial blood gases and and electrolytes performed three
times a day at 4 hourly intervals in two patients diagnosed with Parkinson's
Disease confirmed that the acid base balance and electrolytic equilibrium
suffered changing values. Based on these results and with the purpose of
interfering with the "metabolic alkalosis - metabolic acidosis - respiratory
alkalosis cycle " ( Met Alk - Met Acid - Resp Alk.), the supposed
physicopathogenic mechanism, the patients were treated with Acetazolamide.
Clinical improvement strongly supported the hypothesis which resulted from
treating another patient with ammonium chloride.

Introduction

The summary of a previous article said "Perhaps the changing acid base state
with its inherent metabolic alteration described in the first case, PD stage
3 (pronounced change in the posture, with moderate general motor incapacity)
explains the pathophysiology of Parkinson's disease (PD). Also, the pathology
results and the clinical findings are in close relation with the time of
respiratory alkalosis (Resp Alk), with the reduction of ionic calcium and the
consequent neuromuscular hyperexcitability which involves skeletal and smooth
muscle."

"The fact that clinical tetany does not occur indicates that in the first
stages of the disease there is moderate neuromuscular hyperexcitability. The
aim is to explain how cyclic acid base changes cause the neuromuscular
hyperexcitability. There is no possibility of renal compensation (relief)
since renal compensation occurs after 2-3 days of stable acid base changes.
(The acid-base changes are not stable so renal compensation does not occur.)"

"It has been said  that respiratory compensation of metabolic alkalosis is
practically non existent."

"In considering the second case, stage 5 (complete immobility), it can be said
that the clinical spasm and the state of muscular contraction would be
explained by a major neuromuscular excitability as a result of the
preponderance of the state of metabolic alkalosis."

Casuistic     1st case

MP 71 years of age. No significant personal or family antecedants (history)
The start of her suffering began 1.5 years ago  when a tremor was noted on the
left hand and a stiffness on the right, also salivary incontinence.

Her daughter in law reported that for more than 15 years the patient showed
lack of facial expression. She was treated with carbidopa-levodopa 250 mg three
times a day, and one tablet of hyperiden chlorhydrate daily. Due to intolerance
the carbidopa-levodopa was reduced to 2 times a day. No improvement whatsoever.
Clonidine chlorohydrate of 0.075 mg and chlortalidone were prescribed for the
treatment of moderate hypertension.

The kind of deambulation noted was heavy legs, instability and the need to stop
walking every 10 meters. Micturition no change. Constipated, enemas every 3-4
days. But in the last 4-5 months a difficulty in speaking was noted, and
increased tremor of both lips. Lost 10 kg weight in two years. Deafness in the
left ear. Complains of general weakness and  easily tires. Hoarse voice.

Physical state leathery, seborrheic skin, less pronounced on the forehead.
Present on the eyebrows and the external part of both eyes. Fixed expression.
Does not blink. Movements of the lips mimic the mouth of a fish, loss of
saliva, tremor in tongue, monotonous voice, low and lacking in intensity. The
right hand did not move spontaeneously, tremor of L hand,Tendon reflexes
increased. (Tendon hyperreflexia). Respirations 23 per minute, pulse 78.

Diagnosis Parkinson's disease between clinical stages 1 and 2. They stopped
the clonidina-chlortalidona because the chlortalidone is capable of originating
and maintaining a state of metabolic alkalosis. The laboratory results on 21-1-
85 show: complete hemogram, blood chemistry, enzymes, proteinagram, and
analysis of urine within normal limits.

Results of arterial gases and electrolytes - done at 10:00 hrs, 14:00 hrs and
18:00 hrs of the same day are the following as shown in figure 1- 10:00 hrs pH
7.45, pCO2 29 show Respiratory Alkalosis, the HCO3-  20 and base excess -3 mEq
show a state of Metabolic Acidosis compensating mechanism. pO2 95 mmHg. Anion
not measured (AG) within normal limits. Lactic acid 16 (normal between 6 - 18
mg%) NA+ 140, K+ 4.6, Cl- 111

Figure 2
pH 7.46 pCO2 33 Resp Alk  HCO3- 24 and base excess +0.5. Shows a state of
Respiratory Alkalosis, having the relieving Metabolic Acidosis disappeared.
The AG and the lactic  acid continue within normal limits. pO2 70 mm Hg, K+
3.2. Hypopotassemia through intracellular migration caused by the
uncompensated Respiratory Alkalosis.

Figure 3 H 7.45, pCO2 33, HCO3- 24, excess base +0.5 Same as the previous.
Respiratory Alkalosis no relief. pO2 60, Na+ 148 , K+ 3.1 Cl- 111. Discrete
hypernatraemia and hyperchloraemia with hypopotassemia. The values of pO2 of
95, 70 and 60 showing a decrease into respiratory insufficiency (Respiratory
Insufficiency pO2 between 50 and 80 mm Hg ) until now  of unknown origin. The
lactic acid and AG continue within normal limits.

In summary, the results obtained show a state of Respiratory Alkalosis
relieved (compensated) which at the end of 4 hours was converted to no relief
(compensation), a state which was maintained 4 hours later. It is repeated
that the hypopotassemia is the result of the Respiratory Alkalosis; ignoring
the origin of respiratory insufficiency.

On the basis of the theory confirmed in the publication mentioned, and
inasmuch as  Respiratory Alkalosis by deviation to the left of the
dissociation curve of oxyhaemoglobin is capable of provoking an increase in
Lactic Acid, Metabolizing Lactic Acid increases HCO3- with  consequent
Metabolic Alkalosis and with the deviation to the left of the oxyhaemoglobin
curve will provoke in the same way an increase in lactic acid.

(The oxygen is bound more tightly to haemoglobin and not available to the
tissue. Anaerobic metabolism produces lactic acid. Metabolism of Lactic Acid
increases HCO3- and furthur metabolic alkalosis which binds oygen even more
tightly to haemoglobin)

The use of acetazolamide, strong inhibitor of carbonic anhydrase, is
considered a logical attitude or position, which on preventing the
reabsorbtion of HCO3- at the level of the renal tubes will impede the
Metabolic Alkalosis condition  and at the same time compensate for the
Respiratory Alkalosis.

On May 10 1985 she was prescribed acetazolamide 125 mg twice daily and KCl 12
mEq daily. Followed with carbidopa-levodopa 250 mg twice daily, hyperdino
hydrochloride x 1 and clonidone x 1 for her arterial hypertension.

On May 22 1985 the patient expressed that she felt more comfortable,
enthusiastic and happy, that the stiffness of the right hand lessened, and the
left hand trembled less, without things falling from her hands, spoke better,
and the tongue trembled less and was softer. The  abnormal movement of the
upper lip disappeared, the lower lip feeling less hard, her walking was easier
and more stable and steps more continuous and not hesitant. She was able to do
house chores which she could not do before.

The skin lesions on the forehead, eyebrows and on the external angles (corners)
of both eyes disappeared as well as the leathery/greasy skin. The bowel
movement became practically regular. Her son confirmed the observations, noting
that she was more confident and more lively. The physical examination confirmed
all the results objectively. The tendon hyperreflexia lessened, patient showed
happiness with smiles and laughter, something which was not noted during
previous visits.

The second dose of 125 mg of acetazolamide was stopped. On May 27 1985 the
patient lost the improvement gained before. She was put back to Acetazolamide
125 mg twice daily and with it the improvement was progressively
reestablished.

On July 5th the improvement was maintained, gaining 7 Kg of the weight
previously lost. Respiratory frequency was 18 per minute interval. A third
dose was given of Acetazolamide of approximately 60 mg and the KCl was
increased to 20 mEqu a day.

July 11 1985 the abnormal lip movements totally disappeared. In the
publication mentioned it was suggested that the pathophysiology of Parkinson's
Disease developed as a result of the unavoidable disequilibrium of acid-base
and electrolytes, the installation of the cycle Metabolic Alkalosis-
Metabolic Acidosis- (Lactic Acidosis)- Respiratory Alkalosis, more pronounced
in the patients in the intervening (or middle) evaluative stage.

With regard to the objective of this communication the ionogram and the
arterial gases displayed the authentic instability of the acid-base and
electrolyte equilibrium.

>From the condition of Respiratory Alkalosis with Metabolic Acidosis, in 4
hours converting to uncompensated Respiratory Alkalosis with hypopotassemia
and distinct respiratory insufficiency.

Four hours later the unrelieved respiratory alkalosis was maintained with
hypopotassemia and distinct respiratory insufficiency.

Four hours later the unrelieved Respiratory Alkalosis was maintained with
hypopotassemia and respiratory insufficiency a little more pronounced.
The Respiratory Alkalosis is the cause of the Lactic Acidosis, in Lactic
Acidosis by the metabolism of the Lactic Acid, the HCO3- was increased , which
in sufficient level produced the Metabolic Alkalosis, giving the conditions
for the existence of the previously described cycle.

The clinical improvement obtained with Acetazolamide and KCl validated the
physicopathogenesis mentioned in the original publication. The worsening
occurred with the lessening of the dose of Acetazolamide to half and the
reestablishment of the initial treatment improved the condition. There was
nothing that disproved it, and the Acid- Base and electrolyte changes are
supporting evidence.

As a result of this, in regard to the physical area she uses her capacity to
demonstrate facial state (expression), of mental concentration, anger and
happiness (the patient lost her facial inexpressiveness). In the sensory area
greater sensitivity to temperature when the climate changed. (and better
temperature regulation ? LS)

>From the point of view of the nervous system of the vegetative state the
facial greasiness/leatheriness/seborrhea disappeared. The bowel movement also
becoming regular. The respiratory frequency was 23 per minute interval,
decreasing to 18 per minute interval.

>From the point of view of the nervous system the decrease of the hypertonia of
the lower extremities permitted ambulation without hesitation and with agility.
There was no need to stop the walking movement and then to start again. The
lessening of the stiffness of the left hand permitted the performance of manual
chores which she could not do before. The loss of the (abnormal) movements of
the lips enabled the mouth to be closed, therefore avoiding loss of saliva.

The voice lost the monotony apparent at the start of the treatment. From the
treatment it can be said that the sick person was capable of improving quickly
as mentioned in the results of the prescribed medication on the A-B and
electrolyte equilibrium.

On the other hand, the dynamic condition controls the clinical condition of
these patients, and supposedly the same condition would establish the
anatamopathology which in the stage of total disorganisation, the symptoms
and signs of the disease for which the injury of the secondary organs needed
symptomatic treatment.

The hypothetical physiopathology occurs in three movements. In Lactic Acidosis
glycolysis in anaerobiosis will terminate by a reduction in the reserves of
glycogen.

In Respiratory Alkalosis and metabolic alkalosis the deviation to the left of
the disassociation curve of the oxyhaemoglobin prevents the release of the O2
at the level of the tissue which will have more effect on the Central Nervous
System because of its low reserves of glycogen.

It can also be mentioned that the metabolic changes linked to the "imbalance
of A-B" in the cycle,generate the physicochemical changes responsible for the
emotional changes of the disease e.g. euphoria, insomnia, irritability,
emotional instability, changes in personality, depression, and at times with
changes at the level of the cerebral cortex, dementia conditions may follow.

(It is known that anxiety is produced by Lactate, which supports Ramos'
contention. My view is that the psychological changes are a complex
interaction of dopamine deficiency, dopamine replacement, hypoxia, neurone
loss, and biochemical changes as described by Ramos. LS)

With these metabolic changes the Respiratory Alkalosis is considered
separately. The known effects over the psyche are worth mentioning. For the
effects of Metabolic Alkalosis a brief look at what Ramos, Angel M, has to
say is in order.

Among other considerations, he discusses how millions of patients are exposed
to the risk of suffering mental changes due to Metabolic Alkalosis caused by
the use of diuretics (thiazides, furosemide, ethacrinic acid, mercurials,
corticosteroids, and ACTH.)

The results merit attention because a generalised condition like the cycle
Metabolic Alkalosis- Metabolic Acidosis- (Lactic Acidosis)- Respiratory
Alkalosis produces the knowm pathophysiology and clinical complexity of the
disease including dermatologic, urinary, oesophagus- gastrointestinal
conditions, etc.

It is difficult to understand and much more difficult to accept that they are a
consequence of the classic description of the pathogenesis - the lessening of
the nervous cellules to the level of the nucleus of Rolando, cerelious cells
and other neurectodermal pigmented cells as well as the lessening of the
dopamine in the nervous axons projected over the neo striatum.

In brief, the classic description was only a link in a large chain, many or
all of (the links) are filled in by the proposed cycle. (The cycle fills in
some of the links in the chain of events of which the classic description is
but a part. LS)

In relation to the evolutive possibilities (possible time related changes) of
the cycle there are not two patients with the same or equal clinical evolution
to the state of fatal incapacity varying between 10 and 20 years, sometimes 5
years, speculatively it is said that each patient could suffer a cycle of
variable intensity which in time would be conditioned to the evolutive state
of the disease.

In the presented patient, a case of recent diagnosis, it would seem that the
component of Respiratory Alkalosis predominated. In the first case of the cited
publication, a case of prolonged evolution, the cycle in toto seemed more
evident. In the second case of the same publication .....in the terminal stage
of the disease the metabolic alkalosis component prevailed without doubt,
expressed in a permanent picture of clinical tetany.

Second Case (Observation of progress)

The summary of a therapeutic communication brought up to date - a patient of
66 years of age, with PD diagnosis, with 19 years of evolution and a clinical
course between 4 and 5 evolutive stage. The patient had been surgically
treated in both cerebral hemispheres. The electrolyte and A-B instability and
the cycle Metabolic Alkalosis- Metabolic Acidosis- (Lactic Acidosis)-
Respiratory Alkalosis was confirmed.

The acidifying salt NH4Cl, given with the aim of interfering pharmacologically
(with) the cycle's most accessible component, the Metabolic Alkalosis,
fulfilled its promise. The clinical results up to the present time in their
intermittent form (observations made intermittently over a period of time?) and
with a variable grade and intensity of disease showed truly positive results.

A concomitant clinical worsening and accentuation of the metabolic changes by
excessive medication (alkali for gastric pain?) as well as the clinical
improvement and the decrease of the metabolic changes by reducing the
medication, the A-B instability and the clinical condition would have been
directly related.

The changes of the vegetative nervous system, physical and sensory areas were
of such value that the patient enjoyed real independence, of which she had been
deprived for 1.5 years. The patient was treated with NH4Cl 2g twice daily L-
Dopa-fenserazida 1/2 tablet twice daily. KCl 20 mEq once daily.

The evolution was maintained the same as was mentioned previously. The L-Dopa
fenserazida was continued understanding that its action is on the level of
organic lesion secondary to the physiopathogenic mechanism.

On April 5 1985 a surgical procedure was performed after an accident. Under
anaesthetic there was vomiting and gastric intolerance, all medication was
stopped. The disease predictably fell back to the initial stage of the
treatment.

In these circumstances there was an opportunity to start medication with
Acetazolamide, suspending the NH4Cl. The patient felt progressively better.
In this instance the dose of Acetazolamide was 250 mg per day, with KCl 20 mEq
per day.

Discussion

On continuing the treatment with NH4Cl, the clinical state improved. On
stopping NH4Cl, the condition practically regressed to the pretreatment state..
Upon treating with Acetazolamide, the improvement was restabilised, and was
probably superior to that obtained with NH4Cl. Once more the medication was
appropriate and the truth of the hypothesis was supported

Summary

Two patients with PD were presented. The study of the electrolytes and blood
gases three times in a day at 4 hour intervals demonstrated changes which were
valuable in the management of those patients.

With the aim of changing the pathophysiology they were treated with
Acetazolamide which fulfilled its promise. Clinically there was improvement of
the nervous system and the vegetative nervous system as well as the physical
and sensory areas.

The improvement of the general state of the patients was apparent. It was
apparent that the patients were capable of improving in the way mentioned.
This was possible on the basis that the A-B and electrolyte values changed
state, the changed component prevailed over the static (normal) condition.

The dynamic (changed) condition controlled the clinical disease as well as the
pathologic anatomy which in time caused the symptoms and signs of the disease.
The verification of the hoped for benefit signified the reality of the
pathophysiolgical basis of (Acetazolamide) therapy - a therapy capable of
suppressing the cause of the disease.

These newly emergent diagnostic parameters provide an early diagnosis (of Acid
- Base disturbance) and with it an early therapy that prevents the progression
of the disease.

This new therapy would supplement the present limited symptomatic therapy,
limited in its effect to a general benefit only in trembling, stiffness and
the complex and wide clinical picture that PD presents.

Summary

Two patients with PD and showing an unstable Acid Base balance with related
electrolyte values were treated with Diamox. Both of them showed frank
clinical improvement.

Supposedly the drug interfered with the Metabolic Alkalosis - Metabolic
Acidosis - Respiratory Alkalosis cycle.

Verification of all of the above should signify reality of the described
physiopathogenesis, consequently, diagnostic and therapeutic paramaters and
with them change from a symptomatic to a more rational therapy.

Comment.

As a PD person who has observed many of the effects of PD in myself and
others I am impressed with Ramos' clinical skill. His observations provide an
explanation of hypoxia, lethargy, tremor, aches and pains, exercise
intolerance,and response to Acetazolamide, observations made by myself and
others independent of Ramos. Improvement of the skin condition is intriguing.

The hope of a therapy that slows the progression of PD needs to be further
looked at. Ramos goes as far as to suggest that neurone damage is secondary to
the Respiratory Alkalosis and hypoxia.

Diuretics can cause metabolic alkalosis and diminish the ability of the
kidneys to respond to changes in acid base balance.

The lungs are only able to compensate for alkalosis by breathing slowly to
retain carbon dioxide. The oxygen level suffers in consequence. Recurrent
episodes of hypoxia cause brain damage, esoecially when there is incomplete
recovery between episodes.

PD kidneys may be unable to respond normally to changes in acid base balance
because  hypothalamic and pituitary control is compromised. ACTH, ADH, and
aldosterone may be involved. Aldosterone biosynthesis is inhibited by dopamine;
hypoxia also effects aldosterone levels.

The hypothalamus is easily damaged by hypoxia. Carbon monoxide, viral
infections, mitochondrial damage  and organic phosphates cause hypoxia, and the
hypoxia can cause PD, as well as damaging critical brain funtions such as
memory, movement and hormone funtions.

Alteratively the problem may be similar to that seen in mountain climbing. PD
with hypoxia, or low energy supply, (low ATP), leads to hyperventilation.

Hyperventilation raises oxygen levels, but lowers CO2. Hypoventilation
normalizes the CO2, but the oxygen level falls. Recurrent episodes of hypoxia
lead to permanent damage, making the PD worse, or causing memory loss.

Some PD people are unable to automatically increase pulmonary ventilation with
exercise. They may be able to voluntarily increase ventilation and raise
oxygen levels.

They must remember to breathe in order to exercise. Exercise tests may be
needed to diagnose cases where the response to exercise is present but
diminished. Acidosis, rather than the alkalosis described by Ramos, suggests
diamox be used with caution.

Ramos raises the possibility of improvement in PD by paying attention to acid
base balance and oxygen levels.

83
Author: Bowen BC; Block RE; Sanchez-Ramos J; Pattany PM; and others

Title:          Proton MR spectroscopy of the brain in 14 patients with
                Parkinson disease.

Department of Radiology, University of Miami School of Medicine, FL. AJNR Am J

Neuroradiol 1995 Jan;16(1):61-8

Unique Identifier: MEDLINE 95208543

Abstract:

PURPOSE: To determine whether the proton spectra from patients with clinically
diagnosed Parkinson disease differ from the spectra of age-matched healthy
subjects with respect to the major cerebral metabolite resonances as well as
lactate.

METHODS: Fourteen patients with Parkinson disease (38 to 81 years of age) and
13 healthy control subjects (37 to 81 years of age) were studied using image-
guided, single-voxel (27-cm3 volume) proton MR spectroscopy of the occipital
lobe.

RESULTS: The peak area ratios of N-acetyl aspartate to creatine and N-acetyl
aspartate to choline for Parkinson patients did not show a statistically
significant difference from the corresponding ratios for control subjects.

There was a very significant increase in the ratio of lactate to N-acetyl
aspartate for patients with Parkinson disease, with the greatest increase
(threefold) manifested by the subgroup (n = 4) with dementia.

The difference in N-acetyl aspartate to choline between women (n = 7) with
Parkinson disease and healthy women (n = 9) approached significance. No
dependence of the peak ratios on age, duration of Parkinson disease, or
medication (L-dopa) regimen was found.

CONCLUSION: Preliminary results indicating an increase in cerebral lactate in
patients with Parkinson disease support the hypothesis that Parkinson disease
is a systemic disorder characterized by an impairment of oxidative energy
metabolism.

The larger increases for Parkinson patients with dementia may be diagnostically
useful in assessing clinical course and in differentiating Parkinson disease
from other causes of dementia. Additional studies are needed, though, to
quantitate lactate changes and identify potential contributions from lipid
resonances better.

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