Question 1: Seizures (undiagnosed cause)

Author: Gianpiero Pescarmona
Date: 20/08/2012


Innocentive Forum

The patient suffers from an The patient suffers from an undiagnosed condition, with episodes of malignant high blood pressure and regularly occurring clusters of partial complex seizures.

The Scenario

  • Episodes of malignant high blood pressure
  • Seizures
Both symptoms are dependent on brain poor respiration that depends on multiple factors:
  • Oxygen Availability
    • Oxygen partial pressure (altitude. weather changes)
    • Breath Rate and Deepness (lower during the sleep)
    • Asthma etc
    • Carotid Sinus Syndrome Carotid Sinus Epilepsy
  • Oxygen Transport
    • Blood Hemoglobin
    • MCV (high MCV is associated with slower flow)
  • Oxygen consumption at Mitochondrial level
    • Cyt. C deficiency
      • iron deficiency
      • heme deficiency (low estrogens)
      • hypothyroidism (or resistance to TH)
      • hypoalbuminemia (it affects the protein moiety of Cyt C)
    • Nicotinamide, riboflavin and other B group vitamins
    • Coenzyme Q deficiency (secondary to hypothyroidism)

Whilst the brain hypoxia either localized or diffuse is a well recognised risk factor for these symptoms other risk factors are not usually taken into account:

Low serum sodium

Glucose transport inside the cell is mediated by sodium gradient via carriers belonging to the family of SGLT carriers that comprises Na+-dependent glucose co-transporters (SGLT1 and SGLT2), the glucose sensor SGLT3, the widely distributed inositol and multivitamin transporters SGLT4 and SGLT6,9 and the thyroid iodide transporter SGLT5. Low sodium may result in a strong impairement of nerve and thyroid cells.

Circadian variations of liquor sodium fit with seizures ??

Low adrenals hormones

Cortisol favours gluconeogenesis and sodium reabsorption, hence plays a major role in brain health.
Urinary cortisol alone is not a good marker of daily cortisol production as other derivatives are the real final catabolites. In our lab we perform a multiple analysis that offers more reliable results.

Therefore a Cortisol deficiency is not excluded by the previous tests.

5-alpha-reductase deficiency

This is not a well described syndrome but we have described a patient with seizures and an altered ratio Etiocolan/androstan in the urines suggestive of a reduced synthesis of Neurosteroids : endogenous regulators of the GABAA receptor.

Low glucose or diabetes?

2011-02-20 urinalysis.pdf shows traces of ketones suggesting an unbalance between fat and carbohydrates in the diet

2012-07-09 Hemoglobin A1C immunoassay.pdf: insulin resistance by iron deficiency?

Low heme synthesis

heme synthesis depends mostly on estrogen (or at a lesser extent testosterone) and serum bilirubin can be used as an indirect marker of low heme synthesis.

Bile Pigments in Pulmonary and Vascular Disease, 2012

  • This study revealed a higher risk of myocardial infarction for both men and women associated with low serum BR and low serum albumin

Additional factors


Antiepileptic drugs, hyperhomocysteinemia and B-vitamins supplementation in patients with epilepsy. 2012

  • Elevated total Hcy levels (hyper-tHcy) have been associated with cardiovascular disease in multiple large-scale epidemiologic studies and, in particular, patients with epilepsy exhibit elevated plasma tHcy levels more frequently than the general population caused by polymorphisms in the MTHFR gene and chronic treatment with older antiepileptic drugs.


Lamotrigine can induce a profound change in sex steroid hormones. See Patient 10: Hair Loss

Additional tests required

Transferrin, Transferrin saturation, ferritin
25(OH)Vit D (I did not find the result)
Urinary loss of sodium, potassium, calcium and phosphate (possible tubular defect)

Proposed Therapy

To evaluate the correctness of my metabolic interpretation of these seizures the patient should add to its diet

Vitamin B complex
Coenzyme Q
Iron (if lacking)
Salted crackers (every 2 hours) to supply continuosly brain with glucose and sodium

Even a moderate improvement of symptoms could fortify the hypothesis and without any side effect

2012-08-25T19:16:02 - Gianpiero Pescarmona

Quoted by David Hicks
"A compromised adrenal gland can result in hypoglycaemia which can cause both hypertension and seizures. Hypoglycaemia in the blood; not the adrenal cell; results from the stalled G1 phase regeneration settings."

I fully agree with this statement and also with the suggested diet. Both suggestions are very sound from a biochemical point of view and very similar to what I suggested in my first comment.

Nevertheless many comments focus on immune system and infections. The two approaches are not necessarily in conflict as infections in active phase modify the hormonal pattern.

The extent of this modification depends on the amount of cytokines produced by macrophages and others inflammatory cells. Genetic or nutritional (iron deficiency, triptophan deficiency, vitamin D deficiency) factors are responsible for the extent of inflammation during infections. In many infections (tuberculosi, leprosis, malaria) the symptoms pattern varies according to the iron status. In Africa village nurses know that children are at risk of death for cerebral malaria only when their hemoglobin is under 50 g/l. 1.25 (OH)2 VitD activates macrophages V-ATPase that acidifies macrophage lysosomes necessary for killing of bacteria. Older people has less 1.25 (OH)2 VitD, more cytokines, more infections, worse circulation and more diseases.

A reasonable scheme could be: hypertension and seizures depend on glucose/oxygen deprivation whose regulation depends on steroid hormones that are affected by inflammation secondary to infection, Recurrence of symptoms in cyclic way is typical of infectiuos diseases.

But excessive inflammation depends on host conditions (iron - low in the diet of the mom- calcium, protein . 1.25 (OH)2 VitDvitamin D syntesis is low in iron deficient patients)

2012-08-23T13:48:55 - Gianpiero Pescarmona

from 2011


Macrophage migration inhibitory factor exhibits a pronounced circadian rhythm relevant to its role as a glucocorticoid counter-regulator, 2003

Physiological cortisol circadian rhythm. The figure shows the geometrical mean (light gray line) ± 2 SD values (dark gray lines) of serum cortisol concentration calculated from 20-min samplings over a 24-h period in 33 healthy subjects. The fitted cosinor (black line) is the average of harmonic regressions that were a fit for the individual subject data. Cortisol has a distinct circadian rhythm with a peak of 15.5 μg/dl (95% reference range, 11.7–20.6) occurring at 0832 h and a nadir (time of trough cortisol level) of less than 2.0 μg/dl (95% reference range, 1.5–2.5) at 0018 h. The mean and 95% confidence interval are shown for the mesor (midline estimating statistic of rhythm), acrophase (time of peak using a 24-h clock with 2400 h taken as origin), and nadir. [Reproduced with permission from M. Debono et al.: J Clin Endocrinol Metab 94:1548–1554, 2009 (48 ). © The Endocrine Society.]
The Diagnosis and Management of Central Hypoadrenalism, 2010

Prolactin and cortisol levels in seizure disorders. 1994

Reduced serum level of THDOC, an anticonvulsant steroid, in women with perimenstrual catamenial epilepsy., 2008

Reduced serum level of THDOC, an anticonvulsant steroid, in women with perimenstrual catamenial epilepsy, 2008 PDF

Changes of serum adrenocorticotropic hormone and cortisol levels during sleep seizures. 2008

    Measuring the serum concentrations of adrenocorticotropic hormone (ACTH) and cortisol in epileptic seizures during sleep to investigate their link to the EEG changes.
    Pre-surgical evaluation was performed by video-EEG monitoring using 24 channel recording. Thirty six epilepsy patients could be attributed to two groups: 28 patients had spontaneous seizures, and the other 8 patients whose seizures were induced by bemegride. Another 11 persons with confirmed psychogenic non-epileptic seizures (PNES) served as control group. Blood samples were obtained at five points: wake (08:00 a.m.), sleep (00:00 a.m.), and shortly before, during and after an epileptic seizure. The serum ACTH and cortisol were measured and analyzed by chemiluminescent immunoassay.
    The levels of ACTH and cortisol in serum underwent significant changes: declining below the average sleep-level shortly before seizures , increasing during seizures, and far above the average wake-level after seizures (P < 0.001). Such changes did not occur in the control group (P > 0.05). The ACTH and cortisol levels had no significant difference between spontaneous group and bemegride-induced group (P > 0.05).
    The serum concentrations of ACTH and cortisol during sleep seizures are linked with pre-ictal and ictal EEG changes in epilepsy patients.

Circadian periodicity of brain activity and urinary excretion in the epileptic baboon. 1980

  • A 24-H rhythm in the proclivity of the baboon Papio papio to exhibit a seizure response to intermittent light stimulation (ILS) has been uncovered. Seizure response to ILS was found to be greatest in the morning at about 0900 h, 2 h after lights on, and least severe in the evening at about 2000 h 1 h after lights off. Urine cortisol and potassium excretion rhythms followed the same pattern as seizure susceptibility and sodium rhythms were 3 or 4 delayed. Mean values for urine cortisol per 4 h ranged from 25 microgram/4 h at the maxima (0400 to 0800 h) to 2 microgram/4 h at the minima (2000 to 2400 h). Electrolyte rhythms ranged from 13 to 3 meq/4 h for potassium and 1 to 5 meq/4 h for sodium. Changes in electroencephalographic (EEG) activity also accompanied the change in urine cortisol and potassium, and seizure sensitivity, Changes in the EEG at the diurnal minima (2000 h) consisted of a decrease in slow waves concomitant with an increase in fast activity in the 18-25 Hz range,

Guidelines on the diagnosis and the current management of headache and related disorders, 2011

Corticosteroids (dexamethasone or hydrocortisone) are options for rescue therapy in patients with status migrainosus.

Persistent hypoglycemia due to hyperinsulinemia, hypoglucagonemia and mild adrenal insufficiency. 1987

  • The case history of a patient with serious hypoglycemia (with 0.6-3 mmol/l blood glucose) persisting for eight years and treated as epilepsy during the time of observation is reported. As the cause of hypoglycemia hyperinsulinemia, hypoglucagonemia, and moderate adrenal insufficiency was suggested. The pattern of secretion of insulin as well as of C-peptide indicated, that hyperinsulinemia was induced by hypersecretion of immunoreactive insulin. As the cause of hypersecretion of insulin insulinoma might have been ruled out. Hypoglucagonemia was shown by the low concentration of plasma glucagon. Adrenal insufficiency seemed to be due to ACTH deficiency. Replacement therapy with dexamethasone or administration of ACTH led to elevation of the blood glucose to normal, and the plasma cortisol also reached normal levels. On the basis of other data as well as of our own investigations we suggest a central origin of the illness. The patient has been free from his complaints with normal blood glucose and plasma cortisol concentrations for two years.


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