Dear colleagues, I need some advice in a difficult clinical case.
It's about a young man 34 year old man, diagnosed with Type I diabetes mellitus at the age of 32 years and autoimmune thyroiditis at age 33 years.
Currently, this patient shows complex partial seizures, for what he was induced into barbiturate coma.
After 72 hours, the patient recovered in satisfactory condition and left ICU.
After another 24 hours, the condition worsened again. This patient shows a status epilepticus, complex partial seizures, although persistent anticonvulsant therapy with sodium valproate, which was started at first day of admission in our hospital.
This complex pathologies: Type I Diabetes Mellitus , autoimmune thyroiditis and seizures, can be explained by a autoimmune disorders?
What is your experience in this regard? What would be the tactic of diagnosis and treatment in case of autoimmune diseases?
Hello Vaeceslav, does the patient also show psychiatric or other neulogical abnormalities? Have you considered autoimmune encaphalitis as Hashimoto encephalopathy and performed CSF antibody analysis? From time to time we see such autoimmune encephalopathies in children and adolescents. I remember a case 2 years ago with hashimoto thyreoditis, epilepsy and acute psychiatric abnormalities. Besides negative CSF antibodies and lacking response to steroids we performed repeated plasmapheresis and the patient fully recovered....
Hernán Martínez J, Torres O, Mangual MM, Palermo C, Figueroa C, Santiago M, Miranda Mde L, González E.Hashimoto's encephalopathy: an underdiagnosed clinical entity.Bol Asoc Med P R. 2013;105(1):57-61. Review.
Bien CG, Vincent A.Immune-mediated pediatric epilepsies. Handb Clin Neurol. 2013;111:521-31. doi: 10.1016/B978-0-444-52891-9.00055-5. Review.
Yu HJ, Lee J, Seo DW, Lee M. Clinical Manifestations and Treatment Response of Steroid in Pediatric Hashimoto Encephalopathy. J Child Neurol. 2013 Sep 20;29(7):938-942.
Dear Dr. Wagner, thank you a lot for your advice. Our patient have only epileptic status as neurological manifestation of complex other comorbidities: diabet mellitus 1 and hypothiroidia. What do you think about specific antibodies who may attack pancreas (to develop DM1) and thyroid gland (hypotiroidia) which can be associated with epilepsy?
Hashimoto thyroiditis is associated with Anti-NMDAR encephalitis which may present with refractory or super-refractory status epilepticus.
thyreoid and pancreas antibodies are unlikely mediating the epilepsy though they indicate the presence of further autoantibodies such as anti-NMDAR among others.
Patients of DM 1 and Autoimmune epilepsy may both have anti GAD antibodies. You may investigate your patient for this. I hope you find the attached paper useful.
I wonder why do you define this epilepsy as drug-resistant? Are you sure you gave high enough doses? Did you measure the serum levels of valproate? Was it administered as bolus injections or as continuous infusion? Have you tried levetiracetam or (fos)fenytoin in high enough doses?
Dear Dr. Reimers, you are right: the patient was sub-doses in epileptic treatment or better said was not subjected to sufficient antiepileptic treatment to prevent recurrence of epilepsy. Unfortunately we are unable to dose sodium valproate in plasma.
After second induction of barbiturate coma for cropping status epilepticus, doubled dose of sodium valproate (1800 mg/24 h) was initiated, and no seizures in the last 7 days (EEG control).
On the other hand, another situation puts us in doubt: the etiology of epilepsy in a patient of 34 years old (with no history of seizures), installed with status epilepticus at start ... History of comorbidities as type I diabetes mellitus and autoimmune hypothyroidism we put cautious that treating only symptomatic patients, but not etiology. We can be sure that a patient with suspected autoimmune pathology (in this case suspected anti GAD), an appropriate anti epileptic treatment is enough to prevent epileptic seizures?
I agree that 900 mg/day is a very low dose in status e. I would consider even 1800 mg a moderate dose, but it can of course be sufficient in individual patients. I would not hesitate to start with 2400 mg/day as a continuous infusion in patients with S.E. As to the etiology, well, you will not find out until you have performed more diagnostics wether it is autoimmune or due to other causes. Anyhow, epilepsy treatment is symptomatic in the vast majority of cases, so until you find out more about the etiology and find a possible cure for it, you should not be bothered by this. Until then, I would treat this patient as any other patient with epilepsy: as long as he is seizure-free, do not change treatment and see him 1-2 times a year.
I agree with @ Arne Reimers: the term “refractory” or “therapy-refractory” status epilepticus in my opinion is not very useful regarding the emergency treatment of severe epilepsies and to get any prognosis with prediction accuracy.
I.v sodium valproate is the best way (after barbiturates) to stop the seizures, but after transfer to oral medication we have the seizures again. Maybe the dosis of valproats (per os) is not adequate?
Look for metabolic causes such as non-ketotic hyperglicaemia, hyponatremia. These need to be corrected.
Focal seizures are difficut to control and as previuosly commented increase the Valprovate maximum and even higher than recomended and reduce after seizures are controlled.
autoimmune tiroidities can be associated with hashimoto's enchepahlitis or SREAD ( Encefl, steroids responsive) that can cause status epilepticus. Useful check tyroid hormones and Antibody TPO and TBG, and try a course of steroids or Ig ev ( if steroids not allowed for Diabete).
add phenitoine if VPA doesn't work , or levetiracetam ev .
Is possibile to do do MRI to the patients? In SREAD could be normal or with stroke like lesions.