FiFTEEN MONTHS OF PALLIATIVE DRUG THERAPY WITH EVEN MANGANESE SULPHATE
IN TWO SIBLING WITH NEURAL-AXONAL DYSTROPHY OF HALLERVORDEN-SPATZ.
(Updating, July 2003).
Summary
Genetic and cromosomal anomalies
Drug
modulation of stress reactions
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A mother asked me if an
antistress therapy as habitually I am prescribing could give some relief to two siblings respectively of
21 and of 15 years, at first consultation, both suffering from neural-axonal
dystrophy in the Hallervorden-Spatz variant.
First I specified at once that I could not act
on the fates of these two young persons. Then I asked the mother, treated with
success for a severe depression, if they were present some symptoms that
thought and I think stress symptoms.
According to the
criteria I previously described (index-it):
2. Every illness can have symptoms of
stress as accompanying symptoms besides its direct symptoms.
3. The modulation of stress responses can give
some relief to every illness, even to genetic-chromosomal diseases. (Down' s syndrome; Other genetic or chromosomal anomalies),
After confirming
the presence of several symptoms of stress in both siblings, I decided to
accept them to the consultation, to set up an antistress therapy.
The neural-axonal
dystrophy or the Hallervorden-Spatz disease is a disorder of the movement from
brain degeneration on genetic base, autosomal-recessive type.
The causing gene
has recently been said as PANK2, which is allocated on the chromosome 20. This
corresponds to the pontothenic acid kinase that is essential for the synthesis
of the coenzyme A, by starting from the pantothenic acid or Vit. B5 (Zhou and
coll., 2001).
An overflow of
dopaminergic activation seems even present, as the cause of the psychomotor dysfunction (Chiueh, 2001).
From the clinical
point of view had noticed, besides the progressive dementia, dystonia,
choreoathetosis, muscles' stiffness. In 33% of the cases, spasticity appears, from paraparesis to
spastic tetraparesis with myoclonic movements, and akinesic mutismus
(Wakabayashi and coll., 2000).
Sheeny et al,
1999, reported self-aggression with ulcerations of the labium and of the tongue
have been reported, beginning during periods of intense ore-facial spasms.
The illness onset
can mimic a psychiatric form of schizophrenic type (Gouider-Khouja and coll.,
2000).
I did not find its
correspondent in adult age, even if I am
right to believe that they do not change much.
Now only
palliative medical and surgical therapies exist, with their main aim is the dystonia
(Bruscoli et al., 1998; Sheehy and coll., 1999).
Case histories.
F, nearly 16 years old, suffering from
neural-axonal dystrophy (NAD) of Hallervorden-Spatz, according to diagnosis
made a Lombard neurologic institute. Currently she is in the wheelchair.
06.04.2002: She has nighttime cramps, for which she is
awake 5-10 times every night, and so she wakes her mother who has to succour
her. Other symptoms are atonic constipation, cool hands and feet, high
greediness for sweet things, in particular for chocolate. She bears badly the
confusion, and is worse in the afternoon, so she gets tired. In the mornings
she has hunger at once.
She likes Italian
pasta, but doesn't know if she likes the meat broth. She doesn't have any sore
from decubitus, has fat hair. She needs
more sleep than her brother. The mother does not report any bruxism. She needs
to urinate more often than the brother.
Hairy in face. She drinks if she is thirsty and asks it.
01.06.2002: At
night she sleeps and so permits her mother sleeping. She had cramps 3-4 nights
for week. Now she is less constipated. The temperature of the hands and the
feet is more regulated. Greedy as previously. As for school, according to her
assistant she is going a little better, while the support teacher doesn't see
any improvement. With the new assistant she is doing well. She doesn't longer
need sleeping in the afternoon. Now she chews more easily, has more appetite,
and eats more quickly.
Her hairs are less
fat. She urinates always much. Differences on the menstrual cycle were not
noted. She speaks as first (with difficulty). After a little time of speaking,
she makes herself better understood. She assumed only 100mg carbamazepine,
because with the double dose her labium trembled.
05.07.2003. The manganese sulphate stopped
at once, because the mother attributed it an increase of the dystonic symptoms.
Even the oxcarbamazepine hung, because it increased the myoclonies, and so it
was substituted with 300mg valproate daily. Dystonias have at once
acceleration, for which mow is more rigid, mainly to the face and to the mouth,
for which to eat became difficult, as to swallow. Her weight did get down: She
lost her language. Now she does a vowel complaint nearly continue, that first
she doesn't do. If the weather is changing, she wakes at night. She doesn't
sleep in the afternoon. Currently she is on the wheelchair./span>
Therapeutic variation ( daily doses ).:
Glutamine 250mg, baclofen 20 mg; manganese sulphate 25mg.
M, nearly 21 years old, with neural-axonal
dystrophy of Hallervorden-Spatz (supposed diagnosis in Pavia when he was about
five years and confirmed at 11 years by a Lombard neurologic institute). First
dystonic symptoms appeared when he was 15 months old, after a bronchopulmonary
affection and related antibiotic therapy. Currently in a wheelchair.
06.04.02: If not
he does not have any interest about what one wants to him doing, he inclined to
fold up on himself forward. Hypertonic in flexing, with a carinate thorax. He
has always the rigid hands, and cramps (??) to the left foot.
In past he had
epileptic fits, for which assumes valproate 250mg daily.
He stands badly
noise and confusion. Greedy as first for sweets. His sleeping runs well as
first. Perhaps improved his character, being less impatient.
05.07.2003: Since over four months he
assumes even manganese sulphate in water solution, about 100mg, daily. He is
reacting better, eats better, swallows better, with his bowel function more
regulated, but he has always atonic constipation. No more grimaces. In the Day
Centre that he attends, people say that he is more active, and it is seen in
the drawing. He is much less complaining. He has to feet and legs spasms ( a
little increased ) but he reduced the hyperextension of the hands' phalanxes.
Now he sleeps better and he does an hour and a half sleep in the afternoon.
Some times he wakes at night. More serene, his mood improved, Now he inclined
to the varus position of the legs and feet. Cutaneous eruptions increased.
Therapeutic variation (as a daily dose):
Baclofen 20mg.
Discussion.
The discussion on
this trial of palliative therapy in two
subjects, suffering from neural-axonal dystrophy, Hallervorden-Spatz type,
requires recalling what they have in common and what different.
The duration of
the evident illness, and then its more severe gravity, are decidedly divergent,
at least 19 years for the young man, and not more than 14 years for the girl.
These are stress
symptoms of the girl: Nighttime cramps, atonic constipation, cool hands and
feet, greediness for sweet things, mainly chocolate, reduced threshold for confusion, to be worse in the afternoon,
asthenia, immediate hunger in the mornings, fat hairs, need for sleeping.
In her brother I
found these not specific symptoms of stress: Greediness for sweet things, cool
hands and feet, but with sudden hot flashes, ovesweating, spastic constipation, reduced threshold for
noise and confusion, abnormal reactions to flu vaccinations and to antibiotic
treatments.
Both siblings had
the bases for an antistress therapy, but
the results obtained till now are different, first enough good in the
sister, quite modest in the brother.
Oddly, in the sister
this collateral effect came out even with
the nimodipine, even if with a longer time. Surely, if the EEG features were the same already found in infancy (Nardocci and coll., 1999; Rodriguez
Costa, 2001 ), a slowing drug as valproate should be better, a drug that the
boy kept prescribed and maintained in
therapy.
As antistress drugs
acting on glutamate and GABA I prescribed, pyridoxine, bromazepam and diazepam.
The introduction of the manganese sulphate
as a iron chelating agent (Chiueh, 2001, Direttiva CEE 2001; Recepimento
Direttiva 2001/15/CE, 2003 ), which only the young maintained, seems to have
permitted in this last a switching that has brought relief of many symptoms, probably
allowing the other prescribed drugs to work better. This fact is doubly
interesting, because he was the most severely affected out of both, even in
relationship to his age. In the sister there was an increasing of the dystonic
aspects, as the expected course of the illness, and no improvement during last
eight months. To e</span>Explain this result's difference is not easy.
The brother improvement after manganese introduction, if consequent, would make
a small opening of notable interest.
References.
Bruscoli F., Corsi A., Cavicchi C.,
Carloni R., Ferioli I., Gemmani A., Crociati M., Pompili A.: Obiettivi terapeutici raggiungibili e
strategie terapeutiche utilizzabili, nella NBIA 1 (s. di Hallervorden-Spatz). Minerva Anestesiol 1998, 64: 529-534.
Chiueh CC. Iron overload, oxidative stress, and
axonal dystrophy in brain disorders. Pediatr Neurol 2001, 25: 138-147.
Cocchi R.: Hypo-A-Gaba-erge Depression bei
Kindern. Klinisches Bild und mit neurochemis-ches Mechanismen
Verbundene Symptome. In: Friese H.-J., Trott G.-E. (hrsg): Depression in
Kindheit und in Jugend. Huber, Bern 1988: 126-133.
Cocchi
R.: Sensibilita` alla temperatura ambientale nei soggetti Down: una
indagine su 432 casi. Riv. It. Disturbo Intellet. 1989, 2: 195-199.
Cocchi R. Precursori diretti del glutammato e
del GABA e abitudini alimentari nei Down: Indagine epidemiologica su 460 soggetti. Riv. It. Disturbo Intellet. 1990, 3: 307-312. (English
translation on this site)
DIRETTIVA
2001/15/CE DELLA COMMISSIONE, del 15 febbraio 2001 sulle sostanze che possono
essere aggiunte a scopi nutrizionali specifici ai prodotti alimentari destinati
ad un'alimentazione particolare. Gazzetta ufficiale delle Comunità europee
22.2.2001, L 52/19
Gordon
N. Pantothenate kinase-associated neurodegeneration (Hallervorden-Spatz
syndrome) Eur J Paediatr Neurol 2002, 6: 243-247.
Hickman
SJ; Ward NS; Surtees RA; Stevens JM; Farmer SF. How broad is the phenotype of
Hallervorden-Spatz disease? Acta Neurol Scand 2001, 103: 201-203.
Nardocci N; Zorzi G; Farina L; Binelli S;
Scaioli W; Ciano C; Verga L; Angelini L; Savoiardo M; Bugiani O. Infantile neuroaxonal dystrophy: clinical
spectrum and diagnostic criteria. Neurology
1999, 52:1472-478.
Recepimento direttiva 2001/15/CE sulle
sostanze che possono essere aggiunte a scopi nutrizionali specifici ai prodotti
destinati ad una alimentazione particolare. DL 14 febbraio 2003 n.31,
pubblicato sulla G.U. n. 47 del 26 febbraio 2003.
Scarano V; Pellecchia MT; Filla A; Barone
P. Hallervorden-Spatz syndrome resembling a typical Tourette syndrome. Mov Disord 2002,
17: 618-620.
Swaiman
KF. Hallervorden-Spatz
syndrome. Pediatr Neurol 2001, 25: 102-108
Vaher
U; Napa A; Nurmiste A; Piirsoo A; Sibul H; Talvik T. Four siblings with
Hallervorden-Spatz disease. Brain Dev 2001, 23: 236-239.
Zhou
B; Westaway SK; Levinson B; Johnson MA; Gitschier J; Hayflick SJ. A novel
pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. Nat Genet 2001,
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First published on Internet on Decembre 2002.
Copyright by Renato Cocchi, 2002.
42100 Reggio Emilia
(Italy)
Genetic and cromosomal anomalies
Drug
modulation of stress reactions
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