Re: rls and my neurology appointment; ferritin

[Guest guest]

Hi,

Everyone knew this one would bring me out of the woodwork on the neurologist

and ferritin! The studies thus far are in small numbers; a total of 172.

However, I have talked to other RLS support group facilitators and they

report, as with my mother, those with low ferritin levels when the level comes

up, frequent dramatic improvement of the RLS symptoms. It makes good common

sense once you look into it plus the studies such as Hopkins, are done by

respectable institutions.

So, the neurologist will wait around until someone comes out with a study of

10,000 RLS patients unequivocally confirming the relation between a low

ferritin level and RLS symptoms in the year 2027 while countless suffering

takes place. Look at the facts below and make up your own mind!

My Mother's ferritin level was 8; when it rose to only 13, she experienced an

approximate 50% improvement in her severe RLS symptoms. We are eternally

grateful to the RLS Foundation's Newsletter that brought this possibility to

our attention. Adding my Mom to the below patients in these various studies,

there were 173. Granted a small number but research is just starting to evolve

on RLS.

I suggest have your ferritin level checked and if it is under 50, if okay

with your doctor, take iron supplements and if like my Mom she was not able to

tolerate them, make diet changes rich in iron; dark meat of chicken has 3

times as much iron as white meat, chicken livers are really tasty fried (not

usual health fare, granted), spinach, black strap molasses 1 tablespoon a day

of the brand with 25% of RDA of iron, look at nutritional labels of bread for

ones high iron, etc.

Barbara

RON STATUS AND RESTLESS LEGS SYNDROME

IN THE ELDERLY: 18 RLS patients

Author: OKeeffe ST; Gavin K; Lavan JN

Address: Department of Geriatric Medicine, Beaumont Hospital, Dublin.

Source: Age Ageing, 1994 May, 23:3, 200-3

Abstract: The relationship between iron status and the restless legs syndrome

(RLS) was examined in 18 elderly patients with RLS and in 18 matched control

subjects. A rating scale with a maximum score of 10 was used to assess the

severity of RLS symptoms. Serum ferritin levels were reduced in the RLS

patients compared with control subjects (median 33 micrograms/l vs. 59

micrograms/l, p < 0.01, Wilcoxon signed rank test); serum iron, vitamin B12

and folate levels and haemoglobin levels did not differ between the two

groups.

Serum ferritin levels were inversely correlated with the severity of RLS

symptoms (Spearman's rho -0.53, p < 0.05). Fifteen patients with RLS were

treated with ferrous sulphate for 2 months. RLS severity score improved by a

median value of 4 points in six patients with an initial ferritin < or = 18

micrograms/l, by 3 points in four patients with ferritin > 18 micrograms/l, <

or = 45 micrograms/l and by 1 point in five patients with ferritin > 45

micrograms/l, < 100 micrograms/l. Iron deficiency, with or without anaemia, is

an important contributor to the development of RLS in elderly patients, and

iron supplements can produce a significant reduction in symptoms.

IRON AND THE RESTLESS LEGS SYNDROME: RLS patients 27

Author: Sun ER; Chen CA; Ho G; Earley CJ; RP

Address: s Hopkins University Dept. of Psychology, Baltimore, MD, USA.

Source: Sleep, 1998 Jun 15, 21:4, 371-7

STUDY OBJECTIVES: Using blinded procedures, determine the relation between

serum ferritin levels and severity of subjective and objective symptoms of the

restless legs syndrome (RLS) for a representative patient sample covering the

entire adult age range.

DESIGN: All patient records from the past 4 years were retrospectively

reviewed to obtain data from all cases with RLS. All patients were included

who had ferritin levels obtained at about the same time as a polysomnogram

(PSG), met diagnostic criteria for RLS, and were not on iron or medications

that would reduce the RLS symptoms at the time of the PSG. SETTING: Sleep

Disorders Center.

PATIENTS: 27 (18 females, 9 males), aged 29-81 years.

INTERVENTIONS: None.

MEASUREMENTS AND RESULTS: Measurements included clinical ratings of RLS

severity and PSG measures of sleep efficiency and periodic limb movements

(PLMS) in sleep with and without arousal. Lower ferritin correlated

significantly to greater RLS severity and decreased sleep efficiency. All but

one patient with severe RLS had ferritin levels < or = 50 mcg/l. Patients with

lower ferritin (< or = 50 mcg/l) also showed significantly more PLMS with

arousal than did those with higher ferritin, but the PLMS/hour was not

significantly related to ferritin. This last finding may be due to inclusion

of two 'outliers' or because of severely disturbed sleep of the more severe

RLS patients.

CONCLUSIONS: These data are consistent with those from a prior unblinded study

and suggest that RLS patients will have fewer symptoms if they have ferritin

levels greater than 50 mcg/l.

Periodic Limb Movement Disorder and Iron Deficiency:

126 RLS &/or PLMS Patients

BARAN AS, GOLDBERG R, DIPHILLIPO, MA CURRAN K, FRY JM

Medical College Of Pennsylvania and Hahnemann University, Philadelphia, PA.

It is thought that patients with restless legs syndrome (RLS) are likely to

also have periodic limb movement disorder, although the converse is not

necessarily true. Iron deficiency states have been reported to be associated

with some cases of restless legs syndromel,2, but an association between

periodic limb movement disorder (PLMD) and iron deficiency has not been

identified, to our knowledge. Because of the strong association between RLS

and PLMD, it was hypothesized that iron deficiency plays a role in the

etiology of PLMD. Serum ferritin levels were recommended as part of further

evaluation for patients with the diagnosis of PLMD, with or without RLS,

following polysomnography.

All patients recorded between December 1, 1992 and September 6, 1995 found to

have periodic limb movements greater than or equal to 10 per hour of sleep,

with or without symptoms of RLS were identified. Patients with a concurrent

diagnosis of significant obstructive sleep apnea requiring CPAP were excluded.

Serum ferritin is a sensitive measure of body iron stores. Abnormally low

serum ferritin levels were defined as less than 22 ng/ml, and low normal

levels were defined as falling within the range of 22-25 ng/ml.

Of the 156 patients in whom serum ferritin determination was recommended to

the referring physician and patient laboratory data were available in 37. The

data are presented in the table below.

Patients with PLMD & RLS number (%) Patients with PLMD only number (%) Total

Patients number (%)

Ferritin >25 ng/ml 12 (32.4) 17 (45.9) 29 (78.4)

Ferritin 22-25 ng/ml 2 (5.4) 1 (2.7) 3 (8.1)

Ferritin <22 ng/ml 3 (8.1) 2 (5.4) 5 (13.5)

Total Patients 17 (45.9) 20 (54.1) 37 (100)

We conclude that there may be an association between iron deficiency and PLMD

in the absence of RLS.

Improvement in nocturnal myoclonus and restless legs syndrome after treatment

of iron-deficiency anemia: case report: 1 Severe RLS Patient

POCETA JS, LOUBE DI, HAYDUK R, ERMAN MK

Scripps Clinic and Research Foundation, La Jolla, California, U.S.A .

Restless legs syndrome (RLS), (Ekbom's syndrome) is a condition with

unpleasant leg sensations, often leading to restlessness and sleep disruption.

Nocturnal myoclonus, also called periodic limb movements of sleep (PLMS), is a

movement disorder of repetitive, rhythmic, jerky movements of the legs during

sleep which often accompanies RLS.

The pathophysiology of these conditions is unknown, but there may be an

alteration in central dopamine systems. For example treatment with

dopaminergic agents is usually effective, and RLS has certain similarities to

neuroleptic­induced akathisia. Their appears to be a genetic component as

well. Certain medical conditions appear to predispose to RLS and nocturnal

myoclonus such as neuropathies, uremia, and anemias, but identifiable

causative conditions are not present in the majority of cases.

Ekbom described a series of patients with partial gastrectomy and

iron­deficiency anemia who developed RLS O'Keeffe compared measures of iron

status in a group of elderly patients with RLS to a matched control group and

found that serum ferritin levels were lower in the patient group, even without

anemia. Improvement in RLS symptoms occurred with oral iron repletion.

However, no studies have assessed nocturnal myoclonus in relationship to

iron­deficiency anemia or ill treatment. We report a case of both nocturnal

myoclonus and RLS in which improvement occurred after treatment with

intravenously administered iron.

Case Report. A 47 year­old male complained of 18 months of sleep onset and

sleep maintenance insomnia; associated with a feeling of an inner energy boom.

He had bilateral restlessness of the legs when trying to sleep, punctuated by

jerky movements and a feeling of electrical impulses in the legs. During

sleep, his wife noted repetitive motions of the legs, and sometimes of the

arms.

Seven years previously he had undergone a gastric stapling procedure for

treatment of obesity. His weight initially decreased from about 250 pounds to

200 pounds, but he had gained most of this back. He was taking B­1 injections

prophylactically. The sleep study showed 649 periodic leg movements, which

were of high amplitude with myoclonic onset. He was treated with temazepam and

propoxyphene with fair success. He was found to be anemic and iron deficient,

as described in the Table.

Evaluation found no cause of blood loss, but treatment with oral iron

administration was not effective. He was therefore placed on intravenous iron

infusions which corrected the anemia and normalized serum iron studies. His

symptoms of RLS disappeared, as well as the movements during sleep. Repeat

sleep study showed only 101 periodic leg movements, and a marked decrease in

amplitude of these remaining jerks. He was able to sleep adequately with no

medication.

Biological mechanisms of the effect of iron deficiency on brain biochemistry

and behavior

Author: Youdim MB; Ben-Shachar D; Yehuda S

Address: Department of Pharmacology, Faculty of Medicine, Technion Medical

School, Haifa, Israel.

Source: Am J Clin Nutr, 1989 Sep, 50:3 Suppl, 607-15; discussion 615-7

Abstract: An animal model of nutritional iron deficiency (ID) is described

that demonstrates a reduction of brain nonheme iron. The most prominent

feature of ID is the significant and selective diminution of central dopamine

neurotransmission resulting from the decreased number of dopamine D2 receptors

in the caudate nucleus, nucleus accumbens, pituitary, and in all probability

the frontal cortex. The consequences of diminished dopaminergic

neurotransmission is a modification of dopamine-dependent behaviors and

biochemical reactions, the most important of which is the reduction in

learning processes.

The role of iron in maintaining the homeostasis of normally functioning

dopamine neurons and their involvement in cognitive processes cannot be

excluded. An interference with iron metabolism at an early age can result in

irreversible damage to developing dopamine neurons, with consequences that may

manifest themselves in adult life.

Modulation of dopamine receptor in the striatum by iron: behavioral and

biochemical correlates

Author:Youdim MB; Ashkenazi R; Ben-Shachar D; Yehuda S

Source: Adv Neurol, 1984, 40:, 159-70

Abstract: The present study has shown that in the rat brain iron is unevenly

distributed and may be associated with the dopaminergic neuron. The function

of the large amounts of iron in certain brain areas, such as the pallidum,

caudate nucleus, substantia nigra, nucleus accumbens, and olfactory tubercule,

is not known. But it is obvious that by reduction of brain iron, as in the

case of nutritional iron deficiency, certain dopamine-mediated behavioral

phenomena and biochemical reactions are altered. These changes have been

attributed to the selective reduction in dopamine D2 receptors and function in

brain areas rich in dopamine neurons and iron. If iron is especially important

to dopaminergic modulatory systems in the brain, its deficit might explain the

increasing number of reports on behavioral disturbances, EEG, and event-

related potentials (ERPs) associated with nutritional iron deficiency in

children.

Minimal brain damage induced by early iron deficiency:

modified dopaminergic neurotransmission

Author: Youdim MB; Ben-Shachar D

Source: Isr J Med Sci, 1987 Jan-Feb, 23:1-2, 19-25

Abstract: The reports that iron-deficiency anemia in human subjects induces

behavioral changes was investigated in rats made nutritionally iron-deficient.

The most prominent features of these animals were: the unchanged metabolism of

the neurotransmitters noradrenaline, dopamine and serotonin, profound

reduction of brain nonheme iron, the selective diminution of dopamine D2

receptor number (measured by Bmax), modification of dopamine-dependent

behaviors and reduction of learning processes. The induction of these changes

and their recovery with iron supplementation are age- and time-dependent

phenomena.

In newborn rats, however, the consequences of iron deficiency are

irreversible, even after long-term iron supplementation. The results point to

the profound effect iron metabolism can have on the long-term development and

function of dopaminergic neurotransmission. These findings may not be totally

unexpected, since iron distribution in the brain is highly localized in

dopaminergic-peptidergic regions, such as the globus pallidus, substantia

nigra, red nucleus, thalamus, caudate nucleus and nucleus accumbens. In some

regions its concentration is higher than that found in the liver, the site of

iron metabolism.

Effect of iron chelators on dopamine D2 receptors

Author: Ben-Shachar D; Finberg JP; Youdim MB

Source: J Neurochem, 1985 Oct, 45:4, 999-1005

Abstract: Nutritional iron deficiency induced in rats causes a selective

reduction of [3H]spiperone binding in caudate nucleus. This effect can be

reversed by iron supplementation in vivo. The possibility that iron may be

involved in the dopamine D2 receptor was investigated by examining the effect

of various iron and noniron chelators on the binding of [3H]spiperone in rat

caudate nucleus. Iron chelators 1,10-phenanthroline, 2,4,6-tripyridyl-s-

triazine, alpha, alpha'-dipyridyl, and desferrioxamine mesylate inhibited the

binding of [3H]spiperone.

IRON DEFICIENCY AND THE BRAIN

Author: Parks YA; Wharton BA

Address: Community Health and Mental Handicap Services, Canterbury, UK.

Source: Acta Paediatr Scand Suppl, 1989, 361:, 71-7

Abstract: There is increasing evidence both from 'association' and

'intervention' studies that iron deficiency has an adverse effect on brain

function in animals and children. The severity and duration of iron deficiency

are important in determining the effect on development. Iron replacement

therapy has immediate (within 14 days) and long-term (over 3 months)

beneficial effects on behaviour and psychomotor development. The mechanisms

for this probably involve a number of biochemical pathways in which iron is

essential. These include mitochondrial enzymes and various neurotransmitters.

Cytochrome C is reduced by iron deficiency but brain tissue is relatively

spared until the deficiency is severe. Levels of neurotransmitters such as

noradrenaline, serotonin and dopamine are all altered during iron deficiency

and this may explain some of the behavioural and developmental changes that

occur.