1) Definizione del paziente e della storia
sesso: femminile Data Nascita: 1995
Peso: 52 Statura: 1,68 BMI: **
Anamnesi patologica prossima
Persistono disturbi del carattere e ritardo mentale
Viene fatta diagnosi di porfiria da piombo, in presenza di lieve aumento porfirine urinarie e aumento della eliminazione di piombo dopo trattamento con chelanti.
Anamnesi patologica remota
8 anni: epilessia
- 29/03/2002 primo attacco grave di epilessia con ricovero di una settimana= Depakin Chrono 300 mg ( Valproic Acid). "epilessia morfeiforme" in quanto sopraggiungeva soprattutto in stato di sonno o sonnolenza: E infatti a scuola si annoiava e sonnecchiava.
All'Ospedale XXY, dopo queste crisi avute nonostante il Depakin, si decide di provare con il Tolep. E ha però un rush cutaneo e gonfiore che avrebbe potuto portarla (se in dosi maggiori) ad uno shock anafilattico.
Sempre all'Ospedale XXY si decide allora di passare al farmaco Frisium che però ha effetti devastanti su E: ride come una pazza per ore ed ore a tal punto che non riesce neppure ad addormentarsi dal ridere.
- Si pensa allora di passare al farmaco Gabitril e si tocca il fondo: ha gravi problemi neurologici!Le cascano posate e bicchiere mentre mangia, le tremano le gambe e va tenuta per le ascelle per non farla cadere a terra. La trovo per terra più volte con l'aria stupita... Ha praticamente una forma - visivamente - simile al morbo di Parkinson! Si riprende il Depakin (solo 300 mg), ma ha un'altra crisi. Mi suggeriscono inoltre di provare ad usare il Micronoan rettale in caso di crisi forte.
- altro Istituto dove riconfermano il Depamag, simile al Depakin, ma in dosi maggiori . Da quel momento E non ha più avuto attacchi epilettici e, aumentando di peso per la crescita, siamo arrivati agli attuali 800 mg al giorno. L'istituto le somministra anche il Risperdal in dose 1,75 ml al giorno che però la fa dormire tantissimo, gonfiare e ingrassare. A scuola le mettono così una comoda brandina e più dorme, meno disturba!
CANDIDA vaginale molto fastidiosa da 7 anni (Vaginal Candidosis)
Tagli alle labbra e desquamazione periorale
14 anni: menarca
Depressione grave sia da parte materna che paterna
2) Le basi molecolari degli eventi descritti, tenendo conto di tutti i sintomi ed utilizzando i link alle informazioni pertinenti
Si richiede il profilo steroidi urinari per valutare il quadro ormonale generale
Il dato (analizzando le Kegg Pathways: Steroid hormones Pathway) fa pensare ad una diminuzione della 5-alpha-reductase
PTH <3 (n.r.: 7-65)
Neuroligin and autism
3) Eventuali proposte di terapia, volta al ripristino delle condizioni ottimali
Epilessia trattata fondamentalmente con acido valproico
CANDIDA curata inutilmente con cicli periodici di:
- DIFLUCAN 100 MG (fluconazolo)
- diverse scatole di NISTATINA (che fa inorridire un dermatologo...)
- GSE INTIMO a base di semi di pompelmo
- pomate al cortisone (Advantan)
- MUCOSTOP capsule acquistato negli USA
- Olio di Tea Tee Oil, ecc., ecc.
Papers schizophrenia serum tyrosine
5 alpha steroid reductase deficiency and neurosteroids
The neurosteroid environment in the hippocampus exerts bi-directional effects on seizure susceptibility in mice.
Brain Res. 2008 Dec 3;1243:113-23. Epub 2008 Sep 24.
Gililland-Kaufman KR, Tanchuck MA, Ford MM, Crabbe JC, Beadles-Bohling AS, Snelling C, Mark GP, Finn DA.
The progesterone derivative allopregnanolone (ALLO) rapidly potentiates gamma-aminobutyric acid(A) (GABA) receptor mediated inhibition. The present studies determined whether specific manipulation of neurosteroid levels in the hippocampus would alter seizure susceptibility in an animal model genetically susceptible to severe ethanol (EtOH) withdrawal, Withdrawal Seizure-Prone (WSP) mice. Male WSP mice were surgically implanted with bilateral guide cannulae aimed at the CA1 region of the hippocampus one week prior to measuring seizure susceptibility to the convulsant pentylenetetrazol (PTZ), given via timed tail vein infusion. Bilateral intra-hippocampal infusion of ALLO (0.1 microg/side) was anticonvulsant, increasing the threshold dose of PTZ for onset to myoclonic twitch and face and forelimb clonus by 2- to 3-fold. In contrast, infusion of the 5 alpha-reductase inhibitor finasteride (FIN; 2 microg/side), which decreases endogenous ALLO levels, exhibited a proconvulsant effect . During withdrawal from chronic EtOH exposure, WSP mice were tolerant to the anticonvulsant effect of intra-hippocampal ALLO infusion, consistent with published results following systemic injection. Finally, administration of intra-hippocampal FIN given only during the development of physical dependence significantly increased EtOH withdrawal severity, measured by handling-induced convulsions. These findings are the first demonstration that bi-directional manipulation of hippocampal ALLO levels produces opposite behavioral consequences that are consistent with alterations in GABAergic inhibitory tone in drug-naive mice. Importantly, EtOH withdrawal rendered WSP mice less sensitive to ALLO's anticonvulsant effect and more sensitive to FIN's proconvulsant effect, suggesting an alteration in the sensitivity of hippocampal GABA receptors in response to fluctuations in GABAergic neurosteroids during ethanol withdrawal.
Brain on steroids resists neurodegeneration 2004
L'aumento delle porfirine potrebbe dipendere dal Valproato e non dal Piombo
Levetiracetam in focal epilepsy and hepatic porphyria: a case report. 2004
We report a patient with focal epilepsy and latent hereditary coproporphyria who had exacerbation of clinical symptoms of porphyria under treatment with valproate and primidone and was then treated with levetiracetam without exacerbation of clinically latent porphyria.
Valproate and Porphyria;
Ceruloplasmin, copper (aceruloplasminemia ?)
Aceruloplasminemia. and ferritin 2003
Zolpidem is a potent anticonvulsant in adult and aged mice. 2009 ??
Tests on Platelets
Platelets. 2009 Aug;20(5):328-33.
Investigating GABA and its function in platelets as compared to neurons.
Kaneez FS, Saeed SA.
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270. firstname.lastname@example.org
We have recently suggested that platelets could be used as a model for neuronal receptors. In this paper we have investigated gamma-aminobutyric acid (GABA) metabolism and GABA receptors in platelets and in cultured neurons to see whether platelets' GABA mimics neuronal GABA receptor activities. We used the ELISA technique for detecting the GABA concentration in platelet rich plasma and cultured neurons. The functional effects of GABA and its receptor ligands on platelets were determined using an aggregometer. We found that the GABA concentration is 30% lower in platelets than in neurons and in both preparations GABA was metabolized by GABA transaminase (GABA-T). GABA potentiated calcium dependent platelet aggregation with a higher value in washed platelets suspension (WPS) then in platelet rich plasma (PRP). This effect was inhibited by benzodiazepines, calcium channel blockers and the selective phosphoinositide 3-kinase antagonist Wortmannin. GABA neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. We concluded that platelets could be further developed to be used as a peripheral model to study neuronal GABAergic function and its abnormality in diseases such as epilepsy and schizophrenia. Furthermore our results indicated that PI3-kinase is involved in calcium dependent GABA induced platelet aggregation as this synergistic effect is inhibited by Wortmannin in dose dependent manner.
Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders. 2000
Neurol India. 2000 Sep;48(3):231-8
Ravikumar A, Deepadevi KV, Arun P, Manojkumar V, Kurup PA.
Department of Neurology, Medical College, Trivandrum, and Metabolic Disorders Research Centre, Puliyarakonam, Trivandrum, India.
Catabolism of tryptophan and tyrosine in relation to the isoprenoid pathway was studied in neurological and psychiatric disorders. The concentration of trytophan, quinolinic acid, kynurenic acid, serotonin and 5-hydroxyindoleacetic acid was found to be higher in the plasma of patients with all these disorders; while that of tyrosine, dopamine, epinephrine and norepinephrine was lower . There was increase in free fatty acids and decrease in albumin (factors modulating tryptophan transport) in the plasma of these patients. Concentration of digoxin , a modulator of amino acid transport, and the activity of HMG CoA reductase, which synthesizes digoxin, were higher in these patients; while RBC membrane Na+-K+ ATPase activity showed a decrease. Concentration of plasma ubiquinone (part of which is synthesised from tyrosine) and magnesium was also lower in these patients. No morphine could be detected in the plasma of these patients except in MS. On the other hand, strychnine and nicotine were detectable. These results indicate hypercatabolism of tryptophan and hypocatabolism of tyrosine in these disorders, which could be a consequence of the modulating effect of hypothalamic digoxin on amino acid transport.
Papers diet gaba ketogenic
SSRIs act as selective brain steroidogenic stimulants (SBSSs) at low doses that are inactive on 5-HT reuptake.
Curr Opin Pharmacol. 2009 Feb;9(1):24-30. Epub 2009 Jan 20.
Pinna G, Costa E, Guidotti A.
Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, United States. email@example.com
Brain principal glutamatergic neurons synthesize 3alpha-hydroxy-5alpha-pregnan-20-one (Allo), a neurosteroid that potently, positively, and allosterically modulates GABA action at GABA receptors. Cerebrospinal fluid (CSF) Allo levels are decreased in patients with posttraumatic stress disorder (PTSD) and major depression. This decrease is corrected by fluoxetine in doses that improve depressive symptoms. Emotional-like behavioral dysfunctions (aggression, fear, and anxiety) associated with a decrease of cortico-limbic Allo content can be induced in mice by social isolation. In socially isolated mice, fluoxetine and analogs stereospecifically normalize the decrease of Allo biosynthesis and improve behavioral dysfunctions by a mechanism independent from 5-HT reuptake inhibition. Thus, fluoxetine and related congeners facilitate GABA receptor neurotransmission and effectively ameliorate emotional and anxiety disorders and depression by acting as selective brain steroidogenic stimulants (SBSSs).
Cerebral folate deficiency with developmental delay, autism, and response to folinic acid 2005
One Carbon Metabolism Disturbances and the C667T MTHFR Gene Polymorphism in Children with Autism Spectrum Disorders. 2008