IS THERE SCOPE FOR CHECKING SERUM BIOCHEMISTRY IN THE EPILEPSY CLINIC?
M. E. Farrugia
Department of Neurology, Ninewells Hospital & Medical School, Dundee.
Abstract: We often request blood investigations, almost as a knee-jerk reaction, without asking ourselves why and what we expect to exclude or confirm by doing the test. We often fail to put the patient’s presentation into clinical perspective. Here, we present a scenario where "routine" blood tests were unexpectedly abnormal. A patient presents to the First Fit clinic, having sustained two generalised tonic-clonic epileptic seizures. She was commenced on anti-epileptic medication by her GP prior to being seen by the neurologists.
Routine blood investigations taken in the clinic revealed significant hypocalcaemia. She was investigated for the cause of this biochemical derangement and started on 1-alphahydroxycholecaliferol. Her antiepileptic drug was discontinued once her serum calcium was corrected since she was considered to have symptomatic seizures. The discussion deals with the causesof hypocalcaemia, which is less commonly encountered than hypercalcaemia, and the relevance of checking a patient’s biochemistry in the First Fit clinic. In view of the latter point, there is no clear answer and its use fails to be justified by any strong evidence.
Keywords: Hypocalcaemia; idiopathic hypoparathyroidism; symptomatic epileptic seizures; metabolic derangements; cost utility.
Introduction
We often request "routine" investigations for our patients without considering the chances of that specific test being abnormal or how it would be altering the global management of the patient in question.
In the First Fit clinic, it is important to obtain a reliable witness account in order to confirm whether the event witnessed was indeed a "first fit" and if possible to categorise the epilepsy syndrome. One may opt to request blood tests but the chances of these tests being abnormal or contributory towards the patient’s management is minimal except in the alcoholic population.
Hypocalcaemia is less often encountered in medicine than is hypercalcaemia but may be important in the aetiology of epilepsy. Usually there are clinical features either volunteered by the patient or detected on clinical examination that would make one suspicious of this metabolic derangement.
Our patient presenting to the First Fit clinic was slightly unusual in this respect. There were no abnormal findings on examination and therefore there was no clear indication as to why she ought to have routine blood tests performed. However, these were requested as a matter of routine and surprisingly revealed a significant and profound hypocalcaemia.
The literature is clear in showing that the yield for abnormal blood results in patients presenting in the First Fit clinic is indeed low. However, our case is an example whereby the primary diagnosis and cause for her fits would have been missed had she had not had any blood tests. We suspect that there is no definite answer to this controversial issue and we invite the readers to formulate their opinion regarding this dilemma.
Case report
A 45-year-old lady presented to the epilepsy clinic having sustained two generalised tonic-clonic seizures separated by an interim period of 18months. The first episode was attributed to an element of sleep deprivation while on holiday. Both episodes were witnessed by her husband, who was able to provide a reliable account.
She presented after the second episode to her general practitioner (GP) who commenced her on Lamotrigine and referred her to the First Fit clinic. Her past medical history was unremarkable. Her mother had developed partial epileptic seizures following a cerebrovascular accident. The patient volunteered no symptoms that were of any concern and clinical examination was normal.
In the clinic, routine blood investigations were requested. While her full blood count was normal, her biochemistry revealed a surprisingly low serum calcium of 1.34mmol/L (corrected). She was called back to the ward for further investigations to ascertain the cause of this metabolic derangement. Her phosphate levels were high at 2.01 mmol/L with a normal serum magnesium, albumin and bicarbonate. A full hormonal profile was normal including her thyroid status. Her parathyroid levels were undetectable. 25-hydroxyvitamin D was normal as was her 24hour urinary calcium collection. Her EEG and MRI (brain) were normal, the latter showing no evidence for basal ganglia calcifications.
The biochemical picture was, therefore, in keeping with idiopathic hypoparathyroidism. She was commenced on 1-alpha hydroxycholecalciferol one microgram daily with the plan to withdraw her antiepileptic medication once the calcium levels normalise, since she would be considered to have symptomatic epileptic seizures.
Discussion
It is often considered that the yield for blood investigations in the workup of new-onset seizures is low and their role is often questioned as discussed in papers by Turnbull et al1 and Pellegrino.2 Our patient is an example where the role of biochemistry was undoubtedly useful.
Biochemical disturbances, including hypocalcaemia, can be the precipitant factor in the causation of epileptic seizures. Kayath et al discuss how hypocalcaemia is an important factor in the alcoholic convulsive population since ethanol reduces calcium and magnesium levels.3
There have been various case reports of patients with primary hypoparathyroidism presenting with epilepsy resistant to anti-epileptic medication. The management of these patients obviously includes correction of their hypocalcaemia.4,5 Indeed, epileptic seizures occurring in the context of associated biochemical disturbances necessitate correction of these disturbances as well as a search for the cause of this biochemical upset.
The calcium dynamics are tightly related to those of phosphate and magnesium and it is therefore mandatory to check all three electrolytes as well as the renal function if one detects an abnormality.6 The parathyroid hormone (PTH) levels will indicate if one is dealing with idiopathic or acquired hypoparathyroidism (where parathyroid hormone levels are suppressed).
Alternatively, there may be a mechanism whereby elevated PTH levels are no longer effective as in chronic renal failure, vitamin D deficiency or pseudohypoparathyroidism. In pseudohypoparathyroidism, there is defective binding of PTH to its receptor site or deficient activation of guanyl-nucleotide binding protein with failure to increase intracellular cyclic AMP. Rarely, hypocalcaemia is due to an "overwhelming" of the PTH system as for example in rhabdomyolysis.Hereditary hypoparathyroidism can occur as an isolated entity without any other defects or can be part of a complex hereditary autoimmune polyglandular disorder.
A rare form of hypoparathyroidism is due to congenital aplasia of parathyroid glands, manifest soon after birth. This is the DiGeorge syndrome (or the third and fourth branchial pouch syndrome). Milder incomplete forms have been recognized. As Garabedian discusses, some cases are entirely asymptomatic or present with late-onset or latent hypocalcaemia and have been associated with the chromosome 22q11 microdeletion.7
"Routine biochemistry" is often requested in the First Fit clinic without speculating what the likelihood is of detecting metabolic abnormalities or in what way the results will be altering the patient’s management. Powers studied retrospectively a group of patients presenting to the emergency department over a six month period for evaluation and treatment of recent seizures.8 A total of 88.1% of these patients had serum electrolytes checked. Only 2.4% had seizures primarily due to metabolic derangements. He concluded that patients should be grouped by their medical history to identify those at risk for abnormalities in their biochemistry.
A similar evaluation has been performed by Nypaver et al within the paediatric department.9 In this retrospective study, children with nonfebrile and febrile seizures and between the ages of 2.1 and 5.7 were recruited over a year. They concluded that metabolic abnormalities, (including calcium, glucose and magnesium) rarely contribute towards the aetiology of seizures in children and that these tests are generally costly without contributing towards management. Similar conclusions were attained by Kennery et al, when they studied the utility of these tests again in the paediatric population.10
(1) Suppressed PTH
(a) acquired hypoparathyroidism (secondary to surgery)
(b) idiopathic/ hereditary hypoparathyroidism
(2) Ineffective PTH
(a) chronic renal failure
(b) vitamin D deficiency:
(i) reduced intake
(ii)defective metabolism
(iii) intestinal malabsorption
(iv) Vitamin D dependent rickets
(c) pseudohypoparathyroidism (defective binding of PTH)
(3) PTH overwhelmed as in severe hyperphosphataemia
(a) acute renal failure
(b) rhabdomyolysis
(1) The most important is a good, detailed, reliable witness
account.
(2) An EEG may help with the semiology of the epilepsy but
not necessarily in determining whether the patient has or
has not had an epileptic seizure.
(3) Brain imaging is indicated in investigating patients with
localisation–related epilepsy and is unnecessary in patients
with idiopathic generalized epilepsy. MRI of the brain is the
modality of choice though depends on availability.
A CT scan of the brain will detect some but not necessarily
all focal lesions and has no role in those patients with drug-
resistant epilepsy.
(4) Blood investigations are not usually indicated unless a
metabolic cause is suspected.
Conclusion
In conclusion, we felt that our patient probably suffers from idiopathic hypoparathyroidism and that her epilepsy was secondary to significant hypocalcaemia. Her metabolic abnormality was purely incidental, detected on "blind routine biochemistry".
We have no explanation as to why there was an eighteen month period between the episodes of seizures that she sustained.
The contention remains that the yield for detecting abnormalities in routine serum chemistries is extremely low and that in general, patients presenting to the epilepsy clinic require a clear witness account, a good clinical examination in conjunction with good clinical judgement. The issue remains controversial and there probably is no definite or correct answer. Although the literature is quite clear that checking serum biochemistry is often not useful, it remains a fact that if we had not checked the serum biochemistry in our patient, we would have missed the primary underlying diagnosis.
1 Turnbull TL, Vanden Hoek TL, Howes DS, Eisner RF. Utility of laboratory studies in the emergency department patient with a new-onset seizure. Ann Emerg Med 1990; 19(4):373-77.
2 Pellegrino TR. An emergency department approach to first-time seizures. Emerg Med Clin North Am 1994; 12(4) 925-39.
3 Kayath MJ, Argentoni M, Veira JG. Hypocalcaemia and convulsive syndrome in alcoholics- an association frequently not diagnosed. Rev Assoc Med Bras 1999; 45(1):24-26.
4 Maestripieri P, Vigevano F. Idiopathic hypoparathyroidism and convulsive seizures Riv Neurol 1980; 50(1):56-66.
5 Cox RE. Hypoparathyroidism: an unusual cause of seizures. Ann Emerg Med 1983; 12(5):314-15.
6 Elisaf M, Milionis H, Siamopoulos KC. Hypomagnesemic hypokalemia and hypocalcemia: clinical and laboratory characteristics. Miner Electrolyte Metab 1997; 23(2):105-12.
7 Garabedian M. Hypocalcemia and chromosome 22q11 microdeletion. Genet Couns 1999; 10(4):389-94.
8 Powers RD. Serum chemistry abnormalities in adult patients with seizures. Ann Emerg Med 1985; 14(5):416-420.
9 Nypaver MM, Reynolds SL, Tanz RR, Davis AT. Emergency department laboratory evaluation of children with seizures: dogma or dilemma? Paediatr Emerg Care 1992; 8(1):13-16.
10 Kenney RD, Taylor JA. Absence of serum chemistry abnormalities in pediatric patients presenting with seizures. Paediatr Emerg Care 1992; 8(2):65-66.