- Email: [email protected]
Synergism with GABAergic drugs in refractory epilepsy
By the gel method, 10 sera (3 patients, 7 controls) gave negative reactions with all donor AzB cells. All other reactions were positive, apart from those involving 1 patient’s serum sample that failed to agglutinate all donor A2B cells by the tube method and all donor A2. AlB, and A2B cells by the gel system. Expression of the A antigen on A2B red cells is relatively weak3 and some incompatibilities between group B serum and group AzB donor red cells may be missed by conventional tube methods.4 Our findings suggest that the DiaMed 37°C LISS IAT is less reliable than the immediatespin tube technique at detecting ABO incompatibility between B serum and AzB cells. Several other DiaMed users in the UK have informed us that they are using the 37°C LISS IAT alone to confirm ABO compatibility between donor red cells and patients’ serum. Users should be aware of this limitation of the gel test, and should verify the ABO group of all donor red cell units before transfusion. David Cummins,
Bryan
Downham
Department of Haematology, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK
1 2
Lappiere Y, Rigal D, Adam J, et al. The gel test: a new way to detect red cell antigen-antibody reactions. Transfusion 1990; 30: 109-13. Schonitzer D. The impact of the gel test in routine work. In: DiaMed. Present and future of the gel test, 1st international symposium, Montreux, 1993: 16-20.
3 4
Mollison PL, Engelfriet CP, Contreras M. Blood transfusion in clinical medicine (9th edn). London: Blackwell, 1993. Berry-Dortch S, Woodside CH, Boral LI. Limitations of the immediate spin crossmatch when used for detecting ABO
incompatibility. Transfusion 1985; 25:
176-78.
withdrawn. The patient reported 13 SGTCs over the subsequent three months, only one of which needed hospital admission. The addition of vigabatrin 500 mg at night has effected a further impressive improvement, and he has only four short-lived complex partial seizures (CPS) during the last two months. The second case was a 58-year-old woman, who had epilepsy diagnosed during her first pregnancy at age 22. EEG showed a focus of abnormal activity in the frontotemporal region. CT brain scan was normal. She was receiving sodium valproate 1500 mg and carbamazepine 1600 mg daily, when she was enrolled into a double-blind trial of tiagabine with open follow-up in November, 1992. During the base-line three months of this study, she experienced 52 CPS. When the tiagabine had been titrated to its maximum tolerated dose in this patient (40 mg daily), these were reduced to 17 CPS during the subsequent three months. Since the addition of vigabatrin 500 mg at night two months ago, she has had only 6 CPS. In these two patients with long-standing refractory epilepsy receiving treatment with a regimen containing tiagabine, a "subtherapeutic" dose of vigabatrin4 has resulted in substantial improvement in seizure control. Further increments in vigabatrin dosage are planned. This anecdotal report supports the notion of synergy between GABAergic drugs. We are pursuing this further with laboratory and clinical studies. was
John Paul Leach, Martin J Brodie Epilepsy Research Unit, Department of Medicine & Therapeutics, Western Infirmary, Glasgow G11 6NT, UK 1
Synergism with GABAergic drugs epilepsy
in
refractory
SiR-Previous correspondence in this journale2 and clinical trials elsewhere33 have hinted at the possibility of pharmacological synergism in the management of refractory epilepsy. Drugs that target the same neurotransmitter system may be a logical approach in patients with a solitary seizure type and those with differing modes of action may be complementary in patients who experience a range of seizures. Vigabatrin, a suicide inhibitor of -y-aminobutyric acid (GABA) transaminase activity,. and tiagabine, a GABAreuptake inhibitor,’ have been widely used in our unit, the latter under trial conditions. Two of our patients who had a partial response to tiagabine (reduction in seizure numbers but not abolition) were given a small additional dose of vigabatrin with substantial benefit. In one of these, full-dose vigabatrin had previously been ineffective. The first case was a 28-year-old man who developed epilepsy at the age of 12 after a severe head injury. Surface showed electroencephalography (EEG) epileptiform on the left. Computed tomography discharges anteriorly (CT) of the brain was normal. However, single photon emission CT scanning indicated an area of reduced perfusion in the left frontal lobe. He continued to report many partial seizures, sometimes with automatisms, and secondary generalised tonic-clonic seizures despite treatment with sodium valproate (800 mg daily), carbamazepine (1200 mg daily), and clobazam (20 mg daily). Many other drugs, including vigabatrin 3 g daily, had been unhelpful. He was recruited into an open trial of additional tiagabine in April, 1993. In the two months before starting the drug, he documented 12 secondary generalised tonic-clonic seizures (SGTCs) and had been admitted overnight to his local accident and emergency department on three occasions. When the tiagabine dose reached 40 mg daily, the clobazam 1650
2
3
4
5
Panayiotopoulos CP, Ferrie CD, Knott C, Robinson RO. Interaction of lamotrigine with sodium valproate. Lancet 1993; 341: 445. Pisani F, Di Perri R, Perucca G, Richens A. Interaction of lamotrigine with sodium valproate. Lancet 1993; 341: 1224. Stolarek I, Blacklaw J, Thompson GG, Brodie MJ. Vigabatrin and lamotrigine in refractory epilepsy. J Neurol Neurosurg Psychiatry (in press). Grant SM, Heel RC. Vigabatrin. Drugs 1991; 41: 889-926. Nielsen EB, Suzdac PD, Anderson KE. Characterisation of tiagabine, a new and potent and selective GABA uptake inhibitor. Eur J Pharmacol 1991; 196: 257-66.
The very last word slide SIR-In my
on
the very last minute
last minute slide seldom adds It often provides more detail and less information. A better approach to producing such a slide is to abandon the notion and to spend more time earlier in planning the lecture.
perspective
M F Oliver Royal Brompton
experience, a very presentation.
to a
National Heart &
Lung Institute, London SW3 6LY, UK
CORRECTIONS Pathogenesis of climactenc complaints: ready for the change? In this article by A Oldenhave and C Netelenbos (March 12, p 649), the labelling of the bars on the right in figure 1 should have read "Postmenopause years since LMB" (not premenopause). Cervical pnming with prostaglandin El analogues, misoprostol and gemeprost In this article by H El-Refaey and colleagues (May 14, p 1207), in the Patients and methods section, the final sentence in the first paragraph should have ended: "... a standard difference of 0-75 of the cumulative force required to dilate the cervix". In addition, the first sentence of the second paragraph of this section should have said that misoprostol was given intravaginaly as 600 fLg tablets (not pessaries). Finally, Prof A Templeton’s associated degree is FRCOG and that of D N Wheatley is FRCPath.
Bryan
Downham
Department of Haematology, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK
1 2
Lappiere Y, Rigal D, Adam J, et al. The gel test: a new way to detect red cell antigen-antibody reactions. Transfusion 1990; 30: 109-13. Schonitzer D. The impact of the gel test in routine work. In: DiaMed. Present and future of the gel test, 1st international symposium, Montreux, 1993: 16-20.
3 4
Mollison PL, Engelfriet CP, Contreras M. Blood transfusion in clinical medicine (9th edn). London: Blackwell, 1993. Berry-Dortch S, Woodside CH, Boral LI. Limitations of the immediate spin crossmatch when used for detecting ABO
incompatibility. Transfusion 1985; 25:
176-78.
withdrawn. The patient reported 13 SGTCs over the subsequent three months, only one of which needed hospital admission. The addition of vigabatrin 500 mg at night has effected a further impressive improvement, and he has only four short-lived complex partial seizures (CPS) during the last two months. The second case was a 58-year-old woman, who had epilepsy diagnosed during her first pregnancy at age 22. EEG showed a focus of abnormal activity in the frontotemporal region. CT brain scan was normal. She was receiving sodium valproate 1500 mg and carbamazepine 1600 mg daily, when she was enrolled into a double-blind trial of tiagabine with open follow-up in November, 1992. During the base-line three months of this study, she experienced 52 CPS. When the tiagabine had been titrated to its maximum tolerated dose in this patient (40 mg daily), these were reduced to 17 CPS during the subsequent three months. Since the addition of vigabatrin 500 mg at night two months ago, she has had only 6 CPS. In these two patients with long-standing refractory epilepsy receiving treatment with a regimen containing tiagabine, a "subtherapeutic" dose of vigabatrin4 has resulted in substantial improvement in seizure control. Further increments in vigabatrin dosage are planned. This anecdotal report supports the notion of synergy between GABAergic drugs. We are pursuing this further with laboratory and clinical studies. was
John Paul Leach, Martin J Brodie Epilepsy Research Unit, Department of Medicine & Therapeutics, Western Infirmary, Glasgow G11 6NT, UK 1
Synergism with GABAergic drugs epilepsy
in
refractory
SiR-Previous correspondence in this journale2 and clinical trials elsewhere33 have hinted at the possibility of pharmacological synergism in the management of refractory epilepsy. Drugs that target the same neurotransmitter system may be a logical approach in patients with a solitary seizure type and those with differing modes of action may be complementary in patients who experience a range of seizures. Vigabatrin, a suicide inhibitor of -y-aminobutyric acid (GABA) transaminase activity,. and tiagabine, a GABAreuptake inhibitor,’ have been widely used in our unit, the latter under trial conditions. Two of our patients who had a partial response to tiagabine (reduction in seizure numbers but not abolition) were given a small additional dose of vigabatrin with substantial benefit. In one of these, full-dose vigabatrin had previously been ineffective. The first case was a 28-year-old man who developed epilepsy at the age of 12 after a severe head injury. Surface showed electroencephalography (EEG) epileptiform on the left. Computed tomography discharges anteriorly (CT) of the brain was normal. However, single photon emission CT scanning indicated an area of reduced perfusion in the left frontal lobe. He continued to report many partial seizures, sometimes with automatisms, and secondary generalised tonic-clonic seizures despite treatment with sodium valproate (800 mg daily), carbamazepine (1200 mg daily), and clobazam (20 mg daily). Many other drugs, including vigabatrin 3 g daily, had been unhelpful. He was recruited into an open trial of additional tiagabine in April, 1993. In the two months before starting the drug, he documented 12 secondary generalised tonic-clonic seizures (SGTCs) and had been admitted overnight to his local accident and emergency department on three occasions. When the tiagabine dose reached 40 mg daily, the clobazam 1650
2
3
4
5
Panayiotopoulos CP, Ferrie CD, Knott C, Robinson RO. Interaction of lamotrigine with sodium valproate. Lancet 1993; 341: 445. Pisani F, Di Perri R, Perucca G, Richens A. Interaction of lamotrigine with sodium valproate. Lancet 1993; 341: 1224. Stolarek I, Blacklaw J, Thompson GG, Brodie MJ. Vigabatrin and lamotrigine in refractory epilepsy. J Neurol Neurosurg Psychiatry (in press). Grant SM, Heel RC. Vigabatrin. Drugs 1991; 41: 889-926. Nielsen EB, Suzdac PD, Anderson KE. Characterisation of tiagabine, a new and potent and selective GABA uptake inhibitor. Eur J Pharmacol 1991; 196: 257-66.
The very last word slide SIR-In my
on
the very last minute
last minute slide seldom adds It often provides more detail and less information. A better approach to producing such a slide is to abandon the notion and to spend more time earlier in planning the lecture.
perspective
M F Oliver Royal Brompton
experience, a very presentation.
to a
National Heart &
Lung Institute, London SW3 6LY, UK
CORRECTIONS Pathogenesis of climactenc complaints: ready for the change? In this article by A Oldenhave and C Netelenbos (March 12, p 649), the labelling of the bars on the right in figure 1 should have read "Postmenopause years since LMB" (not premenopause). Cervical pnming with prostaglandin El analogues, misoprostol and gemeprost In this article by H El-Refaey and colleagues (May 14, p 1207), in the Patients and methods section, the final sentence in the first paragraph should have ended: "... a standard difference of 0-75 of the cumulative force required to dilate the cervix". In addition, the first sentence of the second paragraph of this section should have said that misoprostol was given intravaginaly as 600 fLg tablets (not pessaries). Finally, Prof A Templeton’s associated degree is FRCOG and that of D N Wheatley is FRCPath.