A list of aetiologies

The college loves to ask the candidates qestions on the tme of "why is this patient having sizures?". These tend to have some list of biochemistry results, or have a highly suggestive history which leads to a broad range of differentials. One example of such a question is Question 21 from the second paper of 2016, where a young woman presents with seizures after a few days of "unusual behaviour".

Why is she fitting? There are numerous reasons for why one might have a seizure, and of these the majority can (by extension of their magnitude) become causes of status epilepticus. Of course, the most common causes are failure to take one’s own epilepsy tablets.  For the weird causes, there is a good article which lists a massive spectrum of toxins, genetic diseases, rare autoimmune conditions and what have you.

Without further ado, here is a list of possible causes.

Vascular causes:

• Stroke
• Decreased cerebral blood flow: ischaemic encephalopathy
• Increased cerebral blood flow: hypertensive encephalopathy
• Eclampsia falls into this category
• Intracranial haemorrhage – eg. subarachnoid

Infectious causes:

Encephalitis

• Meningitis
• Brain abscess

Neoplastic lesions:

• Space-occupying tumour

Drug-induced status epilepticus

• Sympathomimetics are notorious for this, particularly cocaine and amphetamines.
• Apart from those, one can safely expect status epilepticus to develop from the following drug overdoses:
  • Phenothiazines
  • Tricyclic antidepressants
  • Olanzapine – and you would not need to have a truly massive overdose of this substance- there are case reports of status epilepticus with normal treatment doses, which suggests that it somehow unmasks a tendency towards epilepsy.
  • Isoniazid can cause a status epilepticus in gross overdose due to its effect on vitamin B6, which is a co-factor in GABA synthesis- and frequently the seizures are so vigorous that they are a greater source of lactic acidosis than the inhibition of lactate dehydrogenase . Apparently, the dose required is laughably small, only about 1.5g.
  • Tranexamic acid – although it does appear as if you have to give it directly into the brain in order for it to have that effect. Loading doses as high as 100mg/kg have been used in various studies (that is a humongous 7g for a 70kg male), and the incidence of seizures was only about 3.8%, suggesting that in sensible doses this drug is probably safe.
  • Beta-lactam drugs – particularly cephalosporins and carbapenems – share a structural similarity with the abovementioned epileptogenic baboon-killing bicuculline, and in the context of renal failure they could accumulate to concentrations sufficiently high to induce seziures. Recent data demonstrates that failure to renally adjust a normal dosing regimen will lead to status epilepticus. We have known about this drug reaction for a very long time – the first article reports seizures induced by penicillin which was administered directly into the cerebral ventricles of  experimental animals.

Drug withdrawal:

• From any sort of depressant, but classically from alcohol benzodiazepines and barbiturates. It is generally believed that one should never cease a barbiturate agent abruptly- relentless seizures may ensue.
• The drug withdrawal category also includes the abrupt cessation of (or noncompliance with) regular antiepileptic therapy in a known epileptic.

Idiopathic neurological causes:

• By this, I mean poorly controlled epilepsy. It is possible to be fully compliant with your medications and still find them totally ineffective.

Congenital causes:

• Some people are  extremely unlucky, and suffer from some sort of rare congenital disorder of metabolism which will occasionally surmount their carefully coordinated diet, and flood their brain with toxic metabolic byproducts.
• Alternatively, one can have a structural; congenital abnormality, such as cerebral palsy.

Autoimmune causes:

• Cerebral vasculitis
• NMDA receptor antibodies which are apparently associated with ovarian tumours

Traumatic causes

• Typically, one does not have relentless seizures with trauma. However, seizure disorders in general can develop follwoign head injury, particularly severe ehad injury and situations when something sharp actually penetrates the brain tissue.
• In that sense, neurosurgical procedures could also be viewed as a risk factor.

Endocrine and metabolic causes

• Apart from the abovementioned rare disorders of metabolism, common metabolic disturbances could result in status epilepticus.
• Specifically, Oh’s Manual lists a series of electrolyte distrubances – which are all hypo-something. Hyponatremia, hypokalemia, hypomagnesemia, hypocalcemis – all seem to cause status epilepticus. Why do disorders of electrolyte excess not cause it? No answer is available from the Manual.
• An extremely low or extremely high BSL are equally likely to cause seizures.
• Uremic encephalopathy and hepatic encephalopathy complete the list of metabolic causes.