First clinical experiences about the neurotoxic envenomings inflicted by lowland populations of the Balkan adder, Vipera berus bosniensis Tama ´ s Malina a,b, *, La ´ szlo ´ Krecsa ´k c , Dus ˇan Jelic ´ d , Tomislav Maretic ´ e , Tama ´s To ´ th f , Marijan S ˇ is ˇko g , Nenad Pandak g a Lilly Hungary Ltd., Medical Department, Mada ´ch Imre u. 13-14, H-1075 Budapest, Hungary b University of Szeged, Department of Systematic Zoology and Ecology, Dugonics te ´r 13, H-6722 Szeged, Hungary c Eo ¨tvo ¨s Lora ´nd University, Department of Systematic Zoology and Ecology, Pa ´zma ´ny Pe ´ter s. 1/C, H-1117 Budapest, Hungary d State Institute for Nature Protection, Trg Mazˇuranic ´a 5, 10000 Zagreb, Croatia e University Hospital ‘‘Dr Fran Mihaljevic ´’’, Department of Infectious Disease, Mirogojska 8, 10000 Zagreb, Croatia f Budapest Zoo, Venomous Snake Section, A ´ llatkerti krt. 6-12, H-1146 Budapest, Hungary g General Hospital ‘‘Dr Josip Bencˇevic ´’’, Department of Infectious Disease, Ardrije S ˇ tampara 42, 35000 Slavonski Brod, Croatia 1. Introduction The Common adder (Vipera berus) is the most widespread terrestrial venomous snake species, occurring from Great Britain through Europe (except for the Iberian Peninsula, southern France, central and southern Italy and most part of Greece), and towards east in northern Asia up to Sakhalin. Populations in the Balkans (Croatia, Serbia, Bosnia–Herzegovina, Bulgaria, Macedonia, Mon- tenegro, Albania, and northern Greece) are known as Balkan adders (Vipera berus bosniensis)(Kalyabina-Hauf et al., 2004; Nilson et al., 2005), taxon, which reaches its northernmost distribution in the lowlands of south-western Hungary (Somogy and Zala Counties) at 173–186 m above the sea level (a.s.l.) (Korso ´ s and Krecsa ´ k, 2005). Croatian lowland populations occur at max. 400 m a.s.l. Typical specimens from these lowland populations are shown in Fig. 1, which differ in certain morphological characters and in their ecology from the mountainous populations of V.b. bosniensis and from the nominate form (Maria ´ n, 1956; Korso ´ s and Krecsa ´ k, 2005). In 1927, Reuss described several adders from the valley of the River Sava (Serbia), which he classified into a new genus of Vipera, Mesocoronis, Reuss 1927 (Krecsa ´ k, 2007). Reuss suggested that most of the adder populations in the Balkans (now V.b. bosniensis) possess neurotoxic venom (Krecsa ´ k, 2007). Otto (1930, 1933) investigated adder venoms from the Sava River valley (Serbia), Igman Mountains (Bosnia and Herzegovina) and southern NeuroToxicology 32 (2011) 68–74 ARTICLE INFO Article history: Received 29 May 2010 Accepted 30 November 2010 Available online 8 December 2010 Keywords: Systemic neurotoxicity Cranial nerve paralysis Diplopia Balkan adder ABSTRACT The first overall clinical description of envenomings by the lowland populations of the Balkan adder (Vipera berus bosniensis) is provided by this study. Fifty-four incidents have been collected retrospectively from the south-western Hungarian and the northern Croatian distribution area of the taxon. There were five (9%) asymptomatic, 24 (44%) mild, 12 (22%) moderate, 12 (22%) severe, and one fatal (2%) case according to the Poisoning Severity Score. The single death is a 60-year-old Hungarian case that was caused by V.b. bosniensis. Average hospitalisation was 2.75 days. The most common systemic symptoms were gastrointestinal disorders, ECG changes, persisting hypotension and neurological disorders. The initial phase of neurotoxic manifestations was always expressed in cranial nerve disturbances: ptosis, external ophthalmoplegia, diplopia, reduced focusing capability and blurred vision. Neuromuscular paralysis progressed to dyspnoea and lower limb paralysis in the most severe cases. Unusual symptoms were fluctuating arterial hypertension, drowsiness, and hypokalaemia. Laboratory results reveal leucocytosis, while deviation in the other laboratory values is not common. Envenomings by V.b. bosniensis significantly differ from those by the European adder (Vipera berus berus) in lower manifestation rate of extensive oedema, anaemia, CNS depression, and haematuria but the development of neuromuscular paralysis is high (20%). Their bites rather resulted in mild and moderate local symptoms in envenomed patients than those inflicted by the nominate form. This study presents the evidence of the frequent neurotoxic manifestations in Balkan adder-bitten patients for the first time, which strongly suggests that the venom of the lowland populations of V.b. bosniensis has neurotoxic activity. Crown Copyright ß 2010 Published by Elsevier Inc. All rights reserved. * Corresponding author at: Lilly Hungary Ltd., Mada ´ ch Imre u.13-14, H-1131 Budapest, Hungary. Tel.: +36 20 201 1632; fax: +36 1 328 5103. E-mail address: dyspholidus@gmail.com (T. Malina). Contents lists available at ScienceDirect NeuroToxicology 0161-813X/$ – see front matter . Crown Copyright ß 2010 Published by Elsevier Inc. All rights reserved. doi:10.1016/j.neuro.2010.11.007